rs7764472

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_003322.6(TULP1):c.200C>G(p.Thr67Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.853 in 1,557,490 control chromosomes in the GnomAD database, including 568,033 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.88 ( 59522 hom., cov: 30)

Exomes 𝑓: 0.85 ( 508511 hom. )

Consequence

TULP1
NM_003322.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.430

Publications

33 publications found

Variant links:

Genes affected

TULP1 (HGNC:12423): (TUB like protein 1) This gene encodes a member of the tubby-like gene family (TULPs). Members of this family have been identified in plants, vertebrates, and invertebrates. TULP proteins share a conserved C-terminal region of approximately 200 amino acid residues. The protein encoded by this gene is thought to play a role in the physiology of photoreceptors. Mutations in this gene are associated with recessive juvenile retinitis pigmentosa and Leber congenital amaurosis-15. [provided by RefSeq, Nov 2016]

TULP1 Gene-Disease associations (from GenCC):

retinitis pigmentosa 14
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Leber congenital amaurosis 15
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TULP1 links:

ENSG00000228559 (HGNC:58100):

ENSG00000228559 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 30 curated pathogenic missense variants (we use a threshold of 10). The gene has 7 curated benign missense variants. Gene score misZ: 0.64726 (below the threshold of 3.09). Trascript score misZ: -0.4024 (below the threshold of 3.09). GenCC associations: The gene is linked to retinitis pigmentosa, retinitis pigmentosa 14, Leber congenital amaurosis 15, Leber congenital amaurosis.

BP4

Computational evidence support a benign effect (MetaRNN=6.4844005E-7).

BP6

Variant 6-35511797-G-C is Benign according to our data. Variant chr6-35511797-G-C is described in ClinVar as Benign. ClinVar VariationId is 286865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TULP1	NM_003322.6 link	c.200C>G	p.Thr67Arg	missense_variant	Exon 4 of 15	ENST00000229771.11	NP_003313.3
TULP1	NM_001289395.2 link	c.190+383C>G		intron_variant	Intron 3 of 13		NP_001276324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TULP1	ENST00000229771.11 link	c.200C>G	p.Thr67Arg	missense_variant	Exon 4 of 15	1	NM_003322.6	ENSP00000229771.6

Frequencies

GnomAD3 genomes

AF:

0.883

AC:

134066

AN:

151878

Hom.:

59457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.974

Gnomad AMI

AF:

0.912

Gnomad AMR

AF:

0.890

Gnomad ASJ

AF:

0.817

Gnomad EAS

AF:

0.848

Gnomad SAS

AF:

0.765

Gnomad FIN

AF:

0.820

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.851

Gnomad OTH

AF:

0.861

GnomAD2 exomes

AF:

0.851

AC:

142773

AN:

167774

AF XY:

0.844

show subpopulations

Gnomad AFR exome

AF:

0.977

Gnomad AMR exome

AF:

0.915

Gnomad ASJ exome

AF:

0.807

Gnomad EAS exome

AF:

0.843

Gnomad FIN exome

AF:

0.810

Gnomad NFE exome

AF:

0.853

Gnomad OTH exome

AF:

0.848

GnomAD4 exome

AF:

0.850

AC:

1194417

AN:

1405494

Hom.:

508511

Cov.:

AF XY:

0.847

AC XY:

587026

AN XY:

693450

show subpopulations

African (AFR)

AF:

0.977

AC:

31295

AN:

32024

American (AMR)

AF:

0.911

AC:

34361

AN:

37710

Ashkenazi Jewish (ASJ)

AF:

0.810

AC:

20170

AN:

24908

East Asian (EAS)

AF:

0.853

AC:

31212

AN:

36596

South Asian (SAS)

AF:

0.779

AC:

62219

AN:

79912

European-Finnish (FIN)

AF:

0.817

AC:

39382

AN:

48180

Middle Eastern (MID)

AF:

0.790

AC:

4164

AN:

5272

European-Non Finnish (NFE)

AF:

0.852

AC:

922331

AN:

1082846

Other (OTH)

AF:

0.849

AC:

49283

AN:

58046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

9970

19939

29909

39878

49848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20902

41804

62706

83608

104510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.883

AC:

134195

AN:

151996

Hom.:

59522

Cov.:

AF XY:

0.880

AC XY:

65357

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.974

AC:

40397

AN:

41484

American (AMR)

AF:

0.890

AC:

13621

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.817

AC:

2836

AN:

3472

East Asian (EAS)

AF:

0.848

AC:

4343

AN:

5120

South Asian (SAS)

AF:

0.766

AC:

3691

AN:

4818

European-Finnish (FIN)

AF:

0.820

AC:

8668

AN:

10568

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.851

AC:

57766

AN:

67920

Other (OTH)

AF:

0.860

AC:

1817

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

771

1542

2312

3083

3854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.853

Hom.:

41451

Bravo

AF:

0.896

TwinsUK

AF:

0.854

AC:

3167

ALSPAC

AF:

0.859

AC:

3311

ESP6500AA

AF:

0.969

AC:

4097

ESP6500EA

AF:

0.864

AC:

7196

ExAC

AF:

0.826

AC:

89812

Asia WGS

AF:

0.826

AC:

2870

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 01, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Leber congenital amaurosis 15

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinitis pigmentosa 14

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Retinitis pigmentosa

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.039

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.5

(source)

DANN

Benign

0.19

DEOGEN2

Benign

0.042

T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00046

LIST_S2

Benign

0.16

T;T

MetaRNN

Benign

6.5e-7

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.5

N;.

PhyloP100

-0.43

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.48

N;.

REVEL

Benign

0.18

Sift

Benign

0.90

T;.

Sift4G

Benign

0.68

T;T

Polyphen

0.0

B;.

Vest4

0.079

MPC

0.30

ClinPred

0.00041

GERP RS

0.72

Varity_R

0.039

gMVP

0.16

Mutation Taster

=8/92

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over