chr6-35498009-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003322.6(TULP1):c.*318T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 515,366 control chromosomes in the GnomAD database, including 71,170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.58 ( 28177 hom., cov: 31)

Exomes 𝑓: 0.48 ( 42993 hom. )

Consequence

TULP1
NM_003322.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.216

Publications

23 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:

LOC124901309 (HGNC:):

LOC124901309 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 6-35498009-A-C is Benign according to our data. Variant chr6-35498009-A-C is described in ClinVar as Benign. ClinVar VariationId is 356460.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TULP1	NM_003322.6 link	c.*318T>G	3_prime_UTR_variant	Exon 15 of 15	ENST00000229771.11	NP_003313.3	O00294-1Q0QD38
TULP1	NM_001289395.2 link	c.*318T>G	3_prime_UTR_variant	Exon 14 of 14		NP_001276324.1	O00294-2F1T0I9
LOC124901309	XR_007059561.1 link	n.-124A>C	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TULP1	ENST00000229771.11 link	c.*318T>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_003322.6	ENSP00000229771.6		O00294-1

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

87899

AN:

151456

Hom.:

28127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.869

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.421

Gnomad EAS

AF:

0.588

Gnomad SAS

AF:

0.506

Gnomad FIN

AF:

0.426

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.517

GnomAD4 exome

AF:

0.477

AC:

173485

AN:

363794

Hom.:

42993

Cov.:

AF XY:

0.475

AC XY:

90121

AN XY:

189790

show subpopulations

African (AFR)

AF:

0.864

AC:

9332

AN:

10800

American (AMR)

AF:

0.488

AC:

7706

AN:

15788

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

4632

AN:

11526

East Asian (EAS)

AF:

0.540

AC:

12993

AN:

24046

South Asian (SAS)

AF:

0.492

AC:

19491

AN:

39628

European-Finnish (FIN)

AF:

0.422

AC:

9625

AN:

22804

Middle Eastern (MID)

AF:

0.361

AC:

579

AN:

1602

European-Non Finnish (NFE)

AF:

0.456

AC:

98612

AN:

216338

Other (OTH)

AF:

0.495

AC:

10515

AN:

21262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

4205

8410

12615

16820

21025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

604

1208

1812

2416

3020

<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:

0.581

AC:

88010

AN:

151572

Hom.:

28177

Cov.:

AF XY:

0.577

AC XY:

42751

AN XY:

74068

show subpopulations

African (AFR)

AF:

0.870

AC:

36093

AN:

41500

American (AMR)

AF:

0.514

AC:

7843

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

1454

AN:

3454

East Asian (EAS)

AF:

0.587

AC:

2995

AN:

5098

South Asian (SAS)

AF:

0.507

AC:

2430

AN:

4796

European-Finnish (FIN)

AF:

0.426

AC:

4462

AN:

10484

Middle Eastern (MID)

AF:

0.378

AC:

108

AN:

286

European-Non Finnish (NFE)

AF:

0.459

AC:

31080

AN:

67718

Other (OTH)

AF:

0.519

AC:

1088

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1684

3368

5053

6737

8421

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<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:

0.484

Hom.:

28730

Bravo

AF:

0.598

Asia WGS

AF:

0.550

AC:

1913

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Leber congenital amaurosis 15

Benign:1

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. -

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

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.22

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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