Variant rs112062894 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_001193315.2(VIPAS39):c.598-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

VIPAS39
NM_001193315.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.223

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 -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 14-77443177-G-A is Benign according to our data. Variant chr14-77443177-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261490.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00119 (181/152300) while in subpopulation AFR AF= 0.00423 (176/41574). AF 95% confidence interval is 0.00372. There are 0 homozygotes in gnomad4. There are 99 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIPAS39	NM_001193315.2 link	c.598-25C>T		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 link	c.598-25C>T		intron_variant		1	NM_001193315.2	ENSP00000452191.1		Q9H9C1-1

Frequencies

GnomAD3 genomes

AF:

0.00115

AC:

175

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000279

AC:

AN:

250606

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.00365

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000152

AC:

222

AN:

1461798

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00487

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000662

GnomAD4 genome

AF:

0.00119

AC:

181

AN:

152300

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00423

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000598

Hom.:

Bravo

AF:

0.00113

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.83

CADD

Benign

2.8

DANN

Benign

0.59

BranchPoint Hunter

0.0

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