Variant chr14-77428231-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001193315.2(VIPAS39):c.1461+139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 759,232 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.012 ( 39 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 16 hom. )

Consequence

VIPAS39
NM_001193315.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.826

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:

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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=-0.89).

BP6

Variant 14-77428231-T-C is Benign according to our data. Variant chr14-77428231-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1202490.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1882/152280) while in subpopulation AFR AF= 0.0428 (1778/41560). AF 95% confidence interval is 0.0411. There are 39 homozygotes in gnomad4. There are 897 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIPAS39	NM_001193315.2 linkuse as main transcript	c.1461+139A>G		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.1461+139A>G		intron_variant		1	NM_001193315.2	ENSP00000452191	P1	Q9H9C1-1

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1870

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0426

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0119

GnomAD4 exome

AF:

0.00167

AC:

1012

AN:

606952

Hom.:

AF XY:

0.00141

AC XY:

459

AN XY:

325002

show subpopulations

Gnomad4 AFR exome

AF:

0.0418

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00349

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000158

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000118

Gnomad4 OTH exome

AF:

0.00313

GnomAD4 genome

AF:

0.0124

AC:

1882

AN:

152280

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

897

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0428

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 19, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.9

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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