NM_016485.5:c.787C>T

Variant names:

• chr6-142218506-C-T
• rs761965191
• NM_016485.5:c.787C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016485.5(VTA1):​c.787C>T​(p.Arg263Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000304 in 1,612,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: VTA1 NM_016485.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.77
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23269913).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016485.5. 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
	VTA1	NM_016485.5	MANE Select	c.787C>T	p.Arg263Cys	missense	Exon 8 of 8	NP_057569.2
	VTA1	NM_001286371.2		c.706C>T	p.Arg236Cys	missense	Exon 7 of 7	NP_001273300.1	A0A087WY55
	VTA1	NM_001286372.2		c.532C>T	p.Arg178Cys	missense	Exon 6 of 6	NP_001273301.1	Q9NP79-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VTA1	ENST00000367630.9	TSL:1 MANE Select	c.787C>T	p.Arg263Cys	missense	Exon 8 of 8	ENSP00000356602.3	Q9NP79-1
	VTA1	ENST00000934453.1		c.781C>T	p.Arg261Cys	missense	Exon 8 of 8	ENSP00000604512.1
	VTA1	ENST00000620996.4	TSL:3	c.706C>T	p.Arg236Cys	missense	Exon 7 of 7	ENSP00000481525.1	A0A087WY55

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000960

GnomAD2 exomes AF: 0.0000520 AC: 13 AN: 249830 AF XY: 0.0000444

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000881

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.0000546

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000301 AC: 44 AN: 1460292 Hom.: 0 Cov.: 30 AF XY: 0.0000303 AC XY: 22 AN XY: 726444

African (AFR) AF: 0.0000299 AC: 1 AN: 33396

American (AMR) AF: 0.000157 AC: 7 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.000268 AC: 7 AN: 26112

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 85870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.000179 AC: 1 AN: 5596

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111438

Other (OTH) AF: 0.0000497 AC: 3 AN: 60320

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74386

African (AFR) AF: 0.00 AC: 0 AN: 41524

American (AMR) AF: 0.00 AC: 0 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67980

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.8
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.25
Sift	Uncertain	0.027	D
Sift4G	Benign	0.067	T
Polyphen		0.035	B
Vest4		0.21
MutPred		0.70		Gain of catalytic residue at L264 (P = 0.0101)
MVP		0.44
MPC		0.056
ClinPred		0.21	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.42
Mutation Taster		=47/53	disease causing

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: rs761965191; hg19: chr6-142539643; COSMIC: COSV100859265;