14-77428776-T-C

Variant names:

• chr14-77428776-T-C
• rs2242619
• NM_001193315.2:c.1356+230A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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, G2P, Labcorp Genetics (formerly Invitae)
• arthrogryposis-renal dysfunction-cholestasis syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193315.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIPAS39	NM_001193315.2	MANE Select	c.1356+230A>G		intron	N/A	NP_001180244.1	Q9H9C1-1
	VIPAS39	NM_001193314.2		c.1356+230A>G		intron	N/A	NP_001180243.1	Q9H9C1-1
	VIPAS39	NM_001193317.2		c.1356+230A>G		intron	N/A	NP_001180246.1	Q9H9C1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIPAS39	ENST00000557658.6	TSL:1 MANE Select	c.1356+230A>G		intron	N/A	ENSP00000452191.1	Q9H9C1-1
	VIPAS39	ENST00000343765.6	TSL:1	c.1356+230A>G		intron	N/A	ENSP00000339122.2	Q9H9C1-1
	VIPAS39	ENST00000556412.4	TSL:2	c.1434+230A>G		intron	N/A	ENSP00000451857.1	G3V4K3

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

African (AFR) AF: 0.180 AC: 7477 AN: 41472

American (AMR) AF: 0.477 AC: 7290 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1660 AN: 3468

East Asian (EAS) AF: 0.925 AC: 4790 AN: 5176

South Asian (SAS) AF: 0.507 AC: 2443 AN: 4814

European-Finnish (FIN) AF: 0.537 AC: 5670 AN: 10568

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35534 AN: 67966

Other (OTH) AF: 0.454 AC: 956 AN: 2108

Alfa AF: 0.461 Hom.: 2822

Bravo AF: 0.427

Asia WGS AF: 0.683 AC: 2374 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.8
DANN	Benign	0.63
PhyloP100		-0.031
Mutation Taster		=100/0	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: rs2242619; hg19: chr14-77895119;