rs142958086

chr14-77437793-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001193315.2(VIPAS39):c.836+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00849 in 1,612,554 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.577

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=-0.81).
• BP6: Variant 14-77437793-T-C is Benign according to our data. Variant chr14-77437793-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 261492.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 = 0.00876 (1334/152308) while in subpopulation SAS AF= 0.0367 (177/4826). AF 95% confidence interval is 0.0323. There are 19 homozygotes in gnomad4. There are 631 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIPAS39	NM_001193315.2	c.836+15A>G		intron_variant		ENST00000557658.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIPAS39	ENST00000557658.6	c.836+15A>G		intron_variant		1	NM_001193315.2	P1

Frequencies

GnomAD3 genomes AF: 0.00875 AC: 1331 AN: 152190 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00731

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.0371

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00723

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.0114 AC: 2867 AN: 251378 Hom.: 34 AF XY: 0.0132 AC XY: 1788 AN XY: 135874

Gnomad AFR exome AF: 0.00677

Gnomad AMR exome AF: 0.00483

Gnomad ASJ exome AF: 0.0352

Gnomad EAS exome AF: 0.0107

Gnomad SAS exome AF: 0.0364

Gnomad FIN exome AF: 0.00143

Gnomad NFE exome AF: 0.00711

Gnomad OTH exome AF: 0.0139

GnomAD4 exome AF: 0.00847 AC: 12362 AN: 1460246 Hom.: 141 Cov.: 31 AF XY: 0.00964 AC XY: 7001 AN XY: 726516

Gnomad4 AFR exome AF: 0.00700

Gnomad4 AMR exome AF: 0.00543

Gnomad4 ASJ exome AF: 0.0365

Gnomad4 EAS exome AF: 0.0203

Gnomad4 SAS exome AF: 0.0377

Gnomad4 FIN exome AF: 0.00159

Gnomad4 NFE exome AF: 0.00528

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.00876 AC: 1334 AN: 152308 Hom.: 19 Cov.: 32 AF XY: 0.00847 AC XY: 631 AN XY: 74482

Gnomad4 AFR AF: 0.00741

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.0148

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00723

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.0113 Hom.: 2

Bravo AF: 0.00800

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Significance: Benign/Likely 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 29, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 10, 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	-0.81
Cadd	Benign	4.1
Dann	Benign	0.78

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: rs142958086; hg19: chr14-77904136; COSMIC: COSV58938949; COSMIC: COSV58938949;