rs34835605

chr14-77433822-C-T

Variant summary

Our verdict is Benign. Variant got -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:3
• Conservation: PhyloP100: -1.10

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
VIPAS39	NM_001193315.2	c.1179+20G>A		intron_variant		ENST00000557658.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIPAS39	ENST00000557658.6	c.1179+20G>A		intron_variant		1	NM_001193315.2	P1

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

GnomAD3 exomes AF: 0.186 AC: 46564 AN: 250862 Hom.: 4987 AF XY: 0.189 AC XY: 25624 AN XY: 135568

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 SAS exome AF: 0.250

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

Gnomad4 AFR exome AF: 0.0759

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.00800

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.191

Gnomad4 OTH exome AF: 0.176

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

Gnomad4 AFR AF: 0.0806

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.174

Alfa AF: 0.169 Hom.: 396

Bravo AF: 0.160

Asia WGS AF: 0.126 AC: 441 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 02, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.26
Dann	Benign	0.45

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

Other links and lift over

dbSNP: rs34835605; hg19: chr14-77900165;