14-77428231-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001193315.2(VIPAS39):c.1461+139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00381 in 759,232 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (16 hom.)
• Consequence: VIPAS39 NM_001193315.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.826

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 14-77428231-T-C is Benign according to our data. Variant chr14-77428231-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1202490.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1882/152280) while in subpopulation AFR AF= 0.0428 (1778/41560). AF 95% confidence interval is 0.0411. There are 39 homozygotes in gnomad4. There are 897 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIPAS39	NM_001193315.2	c.1461+139A>G		intron_variant		ENST00000557658.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIPAS39	ENST00000557658.6	c.1461+139A>G		intron_variant		1	NM_001193315.2	P1

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1870 AN: 152162 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0119

GnomAD4 exome AF: 0.00167 AC: 1012 AN: 606952 Hom.: 16 AF XY: 0.00141 AC XY: 459 AN XY: 325002

Gnomad4 AFR exome AF: 0.0418

Gnomad4 AMR exome AF: 0.00235

Gnomad4 ASJ exome AF: 0.00349

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000158

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000118

Gnomad4 OTH exome AF: 0.00313

GnomAD4 genome AF: 0.0124 AC: 1882 AN: 152280 Hom.: 39 Cov.: 32 AF XY: 0.0120 AC XY: 897 AN XY: 74470

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0108 Hom.: 4

Bravo AF: 0.0137

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 19, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.9
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17105786; hg19: chr14-77894574;