rs34835605

Variant names:

• chr14-77433822-C-T
• rs34835605
• NM_001193315.2:c.1179+20G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001193315.2(VIPAS39):​c.1179+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,612,142 control chromosomes in the GnomAD database, including 29,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2248 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27275 hom.)
• Consequence: VIPAS39 NM_001193315.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.10
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• arthrogryposis, renal dysfunction, and cholestasis 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• arthrogryposis-renal dysfunction-cholestasis syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 14-77433822-C-T is Benign according to our data. Variant chr14-77433822-C-T is described in ClinVar as Benign. ClinVar VariationId is 261486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIPAS39	NM_001193315.2	c.1179+20G>A		intron_variant	Intron 16 of 19	ENST00000557658.6	NP_001180244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VIPAS39	ENST00000557658.6	c.1179+20G>A		intron_variant	Intron 16 of 19	1	NM_001193315.2	ENSP00000452191.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23844 AN: 151986 Hom.: 2246 Cov.: 32

Gnomad AFR AF: 0.0807

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.175

GnomAD2 exomes AF: 0.186 AC: 46564 AN: 250862 AF XY: 0.189

Gnomad AFR exome AF: 0.0791

Gnomad AMR exome AF: 0.287

Gnomad ASJ exome AF: 0.149

Gnomad EAS exome AF: 0.00914

Gnomad FIN exome AF: 0.162

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.188 AC: 273988 AN: 1460038 Hom.: 27275 Cov.: 31 AF XY: 0.190 AC XY: 137754 AN XY: 726440

African (AFR) AF: 0.0759 AC: 2538 AN: 33436

American (AMR) AF: 0.277 AC: 12388 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 3895 AN: 26112

East Asian (EAS) AF: 0.00800 AC: 317 AN: 39648

South Asian (SAS) AF: 0.253 AC: 21764 AN: 86130

European-Finnish (FIN) AF: 0.165 AC: 8781 AN: 53358

Middle Eastern (MID) AF: 0.252 AC: 1453 AN: 5756

European-Non Finnish (NFE) AF: 0.191 AC: 212212 AN: 1110610

Other (OTH) AF: 0.176 AC: 10640 AN: 60300

GnomAD4 genome AF: 0.157 AC: 23858 AN: 152104 Hom.: 2248 Cov.: 32 AF XY: 0.157 AC XY: 11680 AN XY: 74344

African (AFR) AF: 0.0806 AC: 3347 AN: 41512

American (AMR) AF: 0.257 AC: 3933 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3470

East Asian (EAS) AF: 0.0164 AC: 85 AN: 5180

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4808

European-Finnish (FIN) AF: 0.147 AC: 1547 AN: 10556

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12800 AN: 67972

Other (OTH) AF: 0.174 AC: 367 AN: 2112

Alfa AF: 0.167 Hom.: 399

Bravo AF: 0.160

Asia WGS AF: 0.126 AC: 441 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Oct 02, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 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	-0.85
CADD	Benign	0.26
DANN	Benign	0.45
PhyloP100		-1.1
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34835605; hg19: chr14-77900165;