6-142198459-G-A

Position:

• chr6-142198459-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016485.5(VTA1):​c.541G>A​(p.Ala181Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VTA1 NM_016485.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.12

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12827751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VTA1	NM_016485.5	c.541G>A	p.Ala181Thr	missense_variant	6/8	ENST00000367630.9	NP_057569.2
VTA1	NM_001286371.2	c.541G>A	p.Ala181Thr	missense_variant	6/7		NP_001273300.1
VTA1	NM_001286372.2	c.367G>A	p.Ala123Thr	missense_variant	5/6		NP_001273301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VTA1	ENST00000367630.9	c.541G>A	p.Ala181Thr	missense_variant	6/8	1	NM_016485.5	ENSP00000356602.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.541G>A (p.A181T) alteration is located in exon 6 (coding exon 6) of the VTA1 gene. This alteration results from a G to A substitution at nucleotide position 541, causing the alanine (A) at amino acid position 181 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.029	.;T;T;.
Eigen	Benign	-0.056
Eigen_PC	Benign	0.0079
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.68	T;T;T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;.;L;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.89	N;.;N;N
REVEL	Benign	0.10
Sift	Benign	0.38	T;.;T;T
Sift4G	Benign	0.50	T;T;T;T
Polyphen		0.067	.;.;B;.
Vest4		0.13
MutPred		0.49		.;Gain of glycosylation at A181 (P = 0.0042);Gain of glycosylation at A181 (P = 0.0042);.;
MVP		0.49
MPC		0.044
ClinPred		0.20	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.039
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-142519596;