Variant 14-77435895-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001193315.2(VIPAS39):c.861C>T(p.Ser287Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,614,080 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 110 hom. )

Consequence

VIPAS39
NM_001193315.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.360

Variant links:

Genes affected

VIPAS39 (HGNC:20347): (VPS33B interacting protein, apical-basolateral polarity regulator, spe-39 homolog) Involved in endosome to lysosome transport and intracellular protein transport. Acts upstream of or within collagen metabolic process and peptidyl-lysine hydroxylation. Located in Golgi apparatus and endosome. Implicated in arthrogryposis, renal dysfunction, and cholestasis 2. [provided by Alliance of Genome Resources, Apr 2022]

VIPAS39 links:

VIPAS39 (HGNC:):

VIPAS39 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 14-77435895-G-A is Benign according to our data. Variant chr14-77435895-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 194427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.36 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00418 (637/152248) while in subpopulation SAS AF= 0.0342 (165/4818). AF 95% confidence interval is 0.03. There are 13 homozygotes in gnomad4. There are 335 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIPAS39	NM_001193315.2 linkuse as main transcript	c.861C>T	p.Ser287Ser	synonymous_variant	13/20	ENST00000557658.6	NP_001180244.1	Q9H9C1-1Q6IA61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIPAS39	ENST00000557658.6 linkuse as main transcript	c.861C>T	p.Ser287Ser	synonymous_variant	13/20	1	NM_001193315.2	ENSP00000452191.1		Q9H9C1-1

Frequencies

GnomAD3 genomes

AF:

0.00420

AC:

639

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.0146

Gnomad SAS

AF:

0.0346

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00272

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00806

AC:

2026

AN:

251378

Hom.:

AF XY:

0.00972

AC XY:

1321

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.0330

Gnomad EAS exome

AF:

0.0107

Gnomad SAS exome

AF:

0.0343

Gnomad FIN exome

AF:

0.00106

Gnomad NFE exome

AF:

0.00267

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.00510

AC:

7462

AN:

1461832

Hom.:

110

Cov.:

AF XY:

0.00620

AC XY:

4507

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00165

Gnomad4 ASJ exome

AF:

0.0344

Gnomad4 EAS exome

AF:

0.0203

Gnomad4 SAS exome

AF:

0.0352

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.00175

Gnomad4 OTH exome

AF:

0.00810

GnomAD4 genome

AF:

0.00418

AC:

637

AN:

152248

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

335

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.0383

Gnomad4 EAS

AF:

0.0147

Gnomad4 SAS

AF:

0.0342

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00272

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.00491

Hom.:

Bravo

AF:

0.00325

Asia WGS

AF:

0.0190

AC:

AN:

3478

EpiCase

AF:

0.00376

EpiControl

AF:

0.00356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 21, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 20, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 26, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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