Variant 14-77428509-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001193315.2(VIPAS39):c.1357-35G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,599,034 control chromosomes in the GnomAD database, including 316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.015 ( 19 hom., cov: 32)

Exomes 𝑓: 0.019 ( 297 hom. )

Consequence

VIPAS39
NM_001193315.2 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0310

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but rather VUS (scored 4 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 14-77428509-C-G is Benign according to our data. Variant chr14-77428509-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 261488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.015 (2288/152266) while in subpopulation NFE AF= 0.0215 (1459/68016). AF 95% confidence interval is 0.0205. There are 19 homozygotes in gnomad4. There are 1100 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIPAS39	NM_001193315.2 linkuse as main transcript	c.1357-35G>C		intron_variant		ENST00000557658.6	NP_001180244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIPAS39	ENST00000557658.6 linkuse as main transcript	c.1357-35G>C		intron_variant		1	NM_001193315.2	ENSP00000452191	P1	Q9H9C1-1

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2289

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00403

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0169

Gnomad ASJ

AF:

0.0181

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.0218

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0214

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.0153

AC:

3775

AN:

246980

Hom.:

AF XY:

0.0156

AC XY:

2081

AN XY:

133582

show subpopulations

Gnomad AFR exome

AF:

0.00349

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.0152

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00395

Gnomad FIN exome

AF:

0.0217

Gnomad NFE exome

AF:

0.0227

Gnomad OTH exome

AF:

0.0190

GnomAD4 exome

AF:

0.0193

AC:

27984

AN:

1446768

Hom.:

297

Cov.:

AF XY:

0.0192

AC XY:

13825

AN XY:

720646

show subpopulations

Gnomad4 AFR exome

AF:

0.00286

Gnomad4 AMR exome

AF:

0.0110

Gnomad4 ASJ exome

AF:

0.0158

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00393

Gnomad4 FIN exome

AF:

0.0201

Gnomad4 NFE exome

AF:

0.0222

Gnomad4 OTH exome

AF:

0.0178

GnomAD4 genome

AF:

0.0150

AC:

2288

AN:

152266

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1100

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00399

Gnomad4 AMR

AF:

0.0169

Gnomad4 ASJ

AF:

0.0181

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.0218

Gnomad4 NFE

AF:

0.0215

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00866

Hom.:

Bravo

AF:

0.0144

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 23, 2019	- -

not specified

Benign:1

Likely 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

-0.86

CADD

Benign

1.4

DANN

Benign

0.78

BranchPoint Hunter

4.0

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