dbSNP rs146288421: VIPAS39:c.1179+13C>G (chr14-77433829-G-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001193315.2(VIPAS39):c.1179+13C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00853 in 1,613,408 control chromosomes in the GnomAD database, including 160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 19 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 141 hom. )

Consequence

VIPAS39
NM_001193315.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.650

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

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 14-77433829-G-C is Benign according to our data. Variant chr14-77433829-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 261485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00881 (1341/152280) while in subpopulation SAS AF= 0.0371 (179/4828). AF 95% confidence interval is 0.0326. There are 19 homozygotes in gnomad4. There are 635 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 rank	MANE	Protein	UniProt
VIPAS39	NM_001193315.2 link	c.1179+13C>G		intron_variant	Intron 16 of 19	ENST00000557658.6	NP_001180244.1	Q9H9C1-1Q6IA61

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VIPAS39	ENST00000557658.6 link	c.1179+13C>G		intron_variant	Intron 16 of 19	1	NM_001193315.2	ENSP00000452191.1		Q9H9C1-1

Frequencies

GnomAD3 genomes

AF:

0.00879

AC:

1338

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00731

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00629

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.0148

Gnomad SAS

AF:

0.0375

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00729

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0114

AC:

2866

AN:

251050

Hom.:

AF XY:

0.0132

AC XY:

1788

AN XY:

135676

show subpopulations

Gnomad AFR exome

AF:

0.00677

Gnomad AMR exome

AF:

0.00483

Gnomad ASJ exome

AF:

0.0353

Gnomad EAS exome

AF:

0.0107

Gnomad SAS exome

AF:

0.0364

Gnomad FIN exome

AF:

0.00143

Gnomad NFE exome

AF:

0.00712

Gnomad OTH exome

AF:

0.0139

GnomAD4 exome

AF:

0.00850

AC:

12419

AN:

1461128

Hom.:

141

Cov.:

AF XY:

0.00968

AC XY:

7033

AN XY:

726892

show subpopulations

Gnomad4 AFR exome

AF:

0.00696

Gnomad4 AMR exome

AF:

0.00544

Gnomad4 ASJ exome

AF:

0.0366

Gnomad4 EAS exome

AF:

0.0203

Gnomad4 SAS exome

AF:

0.0378

Gnomad4 FIN exome

AF:

0.00159

Gnomad4 NFE exome

AF:

0.00531

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.00881

AC:

1341

AN:

152280

Hom.:

Cov.:

AF XY:

0.00853

AC XY:

635

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00741

Gnomad4 AMR

AF:

0.00628

Gnomad4 ASJ

AF:

0.0409

Gnomad4 EAS

AF:

0.0148

Gnomad4 SAS

AF:

0.0371

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00729

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.00801

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 10, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.1

DANN

Benign

0.47

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