Variant rs76396354 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001193315.2(VIPAS39):c.735-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00547 in 1,611,160 control chromosomes in the GnomAD database, including 412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 213 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 199 hom. )

Consequence

VIPAS39
NM_001193315.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.144

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 14-77441138-T-C is Benign according to our data. Variant chr14-77441138-T-C is described in ClinVar as [Benign]. Clinvar id is 261491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0998 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIPAS39	NM_001193315.2 linkuse as main transcript	c.735-45A>G		intron_variant		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.735-45A>G		intron_variant		1	NM_001193315.2	ENSP00000452191.1		Q9H9C1-1

Frequencies

GnomAD3 genomes

AF:

0.0295

AC:

4486

AN:

152142

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00767

AC:

1929

AN:

251402

Hom.:

AF XY:

0.00550

AC XY:

747

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.00512

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000202

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00296

AC:

4325

AN:

1458900

Hom.:

199

Cov.:

AF XY:

0.00255

AC XY:

1849

AN XY:

725860

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.00533

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000114

Gnomad4 OTH exome

AF:

0.00616

GnomAD4 genome

AF:

0.0295

AC:

4492

AN:

152260

Hom.:

213

Cov.:

AF XY:

0.0288

AC XY:

2145

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0115

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0145

Hom.:

Bravo

AF:

0.0336

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 28, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

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

-0.41

CADD

Benign

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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