NM_003322.6:c.200C>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

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 id is 286865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-35511797-G-C is described in Lovd as [Benign].

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	O00294-1Q0QD38
TULP1	NM_001289395.2 link	c.190+383C>G		intron_variant	Intron 3 of 13		NP_001276324.1	O00294-2F1T0I9

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		O00294-1

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

GnomAD3 exomes

AF:

0.851

AC:

142773

AN:

167774

Hom.:

60980

AF XY:

0.844

AC XY:

76863

AN XY:

91076

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 SAS exome

AF:

0.775

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

Gnomad4 AFR exome

AF:

0.977

Gnomad4 AMR exome

AF:

0.911

Gnomad4 ASJ exome

AF:

0.810

Gnomad4 EAS exome

AF:

0.853

Gnomad4 SAS exome

AF:

0.779

Gnomad4 FIN exome

AF:

0.817

Gnomad4 NFE exome

AF:

0.852

Gnomad4 OTH exome

AF:

0.849

GnomAD4 genome

AF:

0.883

AC:

134195

AN:

151996

Hom.:

59522

Cov.:

AF XY:

0.880

AC XY:

65357

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.974

Gnomad4 AMR

AF:

0.890

Gnomad4 ASJ

AF:

0.817

Gnomad4 EAS

AF:

0.848

Gnomad4 SAS

AF:

0.766

Gnomad4 FIN

AF:

0.820

Gnomad4 NFE

AF:

0.851

Gnomad4 OTH

AF:

0.860

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

- -

Apr 01, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

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

- -

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

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;.

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over