chr14-77428776-T-C

Position:

• chr14-77428776-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001193315.2(VIPAS39):​c.1356+230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,060 control chromosomes in the GnomAD database, including 16,954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.44 (16954 hom., cov: 32)
• Consequence: VIPAS39 NM_001193315.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0310

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=-0.83).
• BP6: Variant 14-77428776-T-C is Benign according to our data. Variant chr14-77428776-T-C is described in ClinVar as [Benign]. Clinvar id is 1221479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIPAS39	NM_001193315.2	c.1356+230A>G		intron_variant		ENST00000557658.6	NP_001180244.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIPAS39	ENST00000557658.6	c.1356+230A>G		intron_variant		1	NM_001193315.2	ENSP00000452191	P1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66527 AN: 151942 Hom.: 16946 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.447

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.438 AC: 66547 AN: 152060 Hom.: 16954 Cov.: 32 AF XY: 0.443 AC XY: 32900 AN XY: 74334

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.925

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.454

Alfa AF: 0.470 Hom.: 2813

Bravo AF: 0.427

Asia WGS AF: 0.683 AC: 2374 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.63

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: rs2242619; hg19: chr14-77895119;