rs225634

Variant names:

• chr6-142155482-A-T
• rs225634
• NM_016485.5:c.112+8083A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016485.5(VTA1):​c.112+8083A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,024 control chromosomes in the GnomAD database, including 10,403 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (10403 hom., cov: 32)
• Consequence: VTA1 NM_016485.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493
• Publications: 4 publications found

Genes affected

VTA1 (HGNC:20954): (vesicle trafficking 1) C6ORF55 encodes a protein involved in trafficking of the multivesicular body, an endosomal compartment involved in sorting membrane proteins for degradation in lysosomes (Ward et al., 2005 [PubMed 15644320]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTA1	NM_016485.5	c.112+8083A>T		intron_variant	Intron 1 of 7	ENST00000367630.9	NP_057569.2
VTA1	NM_001286371.2	c.112+8083A>T		intron_variant	Intron 1 of 6		NP_001273300.1
VTA1	NM_001286372.2	c.33+8083A>T		intron_variant	Intron 1 of 5		NP_001273301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTA1	ENST00000367630.9	c.112+8083A>T		intron_variant	Intron 1 of 7	1	NM_016485.5	ENSP00000356602.3
VTA1	ENST00000620996.4	c.112+8083A>T		intron_variant	Intron 1 of 6	3		ENSP00000481525.1
VTA1	ENST00000367621.1	c.33+8083A>T		intron_variant	Intron 1 of 6	5		ENSP00000356593.1
VTA1	ENST00000452973.6	c.33+8083A>T		intron_variant	Intron 1 of 5	2		ENSP00000395767.2

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51659 AN: 151904 Hom.: 10407 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.348

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

GnomAD4 genome AF: 0.340 AC: 51653 AN: 152024 Hom.: 10403 Cov.: 32 AF XY: 0.334 AC XY: 24828 AN XY: 74292

African (AFR) AF: 0.146 AC: 6056 AN: 41486

American (AMR) AF: 0.294 AC: 4495 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2067 AN: 3472

East Asian (EAS) AF: 0.145 AC: 755 AN: 5190

South Asian (SAS) AF: 0.421 AC: 2031 AN: 4828

European-Finnish (FIN) AF: 0.371 AC: 3915 AN: 10540

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31050 AN: 67920

Other (OTH) AF: 0.347 AC: 733 AN: 2110

Alfa AF: 0.388 Hom.: 1572

Bravo AF: 0.320

Asia WGS AF: 0.268 AC: 937 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.73
PhyloP100		0.49
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: rs225634; hg19: chr6-142476619;