rs750350264

Variant names:

• chr6-142166275-C-A
• rs750350264
• NM_016485.5:c.160C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-142166275-C-A
• chr6-142166275-C-T

Variant summary

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

The NM_016485.5(VTA1):​c.160C>A​(p.Pro54Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,112 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P54S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: VTA1 NM_016485.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.78

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTA1	NM_016485.5	c.160C>A	p.Pro54Thr	missense_variant	Exon 2 of 8	ENST00000367630.9	NP_057569.2
VTA1	NM_001286371.2	c.160C>A	p.Pro54Thr	missense_variant	Exon 2 of 7		NP_001273300.1
VTA1	NM_001286372.2	c.34-3275C>A		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.160C>A	p.Pro54Thr	missense_variant	Exon 2 of 8	1	NM_016485.5	ENSP00000356602.3
VTA1	ENST00000620996.4	c.160C>A	p.Pro54Thr	missense_variant	Exon 2 of 7	3		ENSP00000481525.1
VTA1	ENST00000367621.1	c.34-3275C>A		intron_variant	Intron 1 of 6	5		ENSP00000356593.1
VTA1	ENST00000452973.6	c.34-3275C>A		intron_variant	Intron 1 of 5	2		ENSP00000395767.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250814 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135574

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460112 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726402

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000564 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	0.0063	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	.;M
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-4.8	.;D
REVEL	Benign	0.23
Sift	Benign	0.031	.;D
Sift4G	Uncertain	0.059	T;T
Polyphen		0.65	.;P
Vest4		0.72
MutPred		0.32		Gain of MoRF binding (P = 0.0497);Gain of MoRF binding (P = 0.0497);
MVP		0.56
MPC		0.30
ClinPred		0.96	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.71
gMVP		0.35

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: rs750350264; hg19: chr6-142487412;