chr6-142147339-C-T

Position:

• chr6-142147339-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP5_Moderate

The NM_016485.5(VTA1):​c.52C>T​(p.Gln18*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VTA1 NM_016485.5 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.96

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-142147339-C-T is Pathogenic according to our data. Variant chr6-142147339-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3064210.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VTA1	NM_016485.5	c.52C>T	p.Gln18*	stop_gained	1/8	ENST00000367630.9	NP_057569.2
VTA1	NM_001286371.2	c.52C>T	p.Gln18*	stop_gained	1/7		NP_001273300.1
VTA1	NM_001286372.2	c.-28C>T		5_prime_UTR_variant	1/6		NP_001273301.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VTA1	ENST00000367630.9	c.52C>T	p.Gln18*	stop_gained	1/8	1	NM_016485.5	ENSP00000356602.3
VTA1	ENST00000620996.4	c.52C>T	p.Gln18*	stop_gained	1/7	3		ENSP00000481525.1
VTA1	ENST00000367621.1	c.-28C>T		5_prime_UTR_variant	1/7	5		ENSP00000356593.1
VTA1	ENST00000452973.6	c.-28C>T		5_prime_UTR_variant	1/6	2		ENSP00000395767.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Mar 17, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	49
DANN	Uncertain	1.0
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Benign	0.62	D
Vest4		0.71
GERP RS		5.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

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: chr6-142468476;