Variant rs1051952 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TULP1	NM_003322.6 linkuse as main transcript	c.*318T>G		3_prime_UTR_variant	15/15	ENST00000229771.11	NP_003313.3
TULP1	NM_001289395.2 linkuse as main transcript	c.*318T>G		3_prime_UTR_variant	14/14		NP_001276324.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TULP1	ENST00000229771.11 linkuse as main transcript	c.*318T>G	3_prime_UTR_variant	15/15	1	NM_003322.6	ENSP00000229771	P4	O00294-1
TULP1	ENST00000322263.8 linkuse as main transcript	c.*318T>G	3_prime_UTR_variant	14/14	1		ENSP00000319414	A2	O00294-2
TULP1	ENST00000614066.4 linkuse as main transcript	c.*318T>G	3_prime_UTR_variant	14/14	5		ENSP00000477534	A2

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

Gnomad4 AFR exome

AF:

0.864

Gnomad4 AMR exome

AF:

0.488

Gnomad4 ASJ exome

AF:

0.402

Gnomad4 EAS exome

AF:

0.540

Gnomad4 SAS exome

AF:

0.492

Gnomad4 FIN exome

AF:

0.422

Gnomad4 NFE exome

AF:

0.456

Gnomad4 OTH exome

AF:

0.495

GnomAD4 genome

AF:

0.581

AC:

88010

AN:

151572

Hom.:

28177

Cov.:

AF XY:

0.577

AC XY:

42751

AN XY:

74068

show subpopulations

Gnomad4 AFR

AF:

0.870

Gnomad4 AMR

AF:

0.514

Gnomad4 ASJ

AF:

0.421

Gnomad4 EAS

AF:

0.587

Gnomad4 SAS

AF:

0.507

Gnomad4 FIN

AF:

0.426

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.519

Alfa

AF:

0.474

Hom.:

18663

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.75

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

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