6-142147339-C-T

Variant names:

• chr6-142147339-C-T
• NM_016485.5:c.52C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 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]

NMBR (HGNC:7843): (neuromedin B receptor) This gene encodes a 7-transmembrane G protein-coupled receptor that binds neuromedin B, which is a growth factor and mitogen for gastrointestinal epithelial tissue and for normal and neoplastic lung. This receptor may play a role in smooth muscle contraction, neuronal responses, and the regulation of cell growth. Antagonists of this receptor have a potential therapeutic use in inhibiting tumor cell growth. Polymorphisms in this gene may be associated with a susceptibility for schizophrenia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 VariationId is 3064210.Status of the report is criteria_provided_single_submitter, 1 stars.

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.52C>T	p.Gln18*	stop_gained	Exon 1 of 8	NP_057569.2
	VTA1	NM_001286371.2		c.52C>T	p.Gln18*	stop_gained	Exon 1 of 7	NP_001273300.1	A0A087WY55
	VTA1	NM_001286372.2		c.-28C>T		5_prime_UTR	Exon 1 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.52C>T	p.Gln18*	stop_gained	Exon 1 of 8	ENSP00000356602.3	Q9NP79-1
	VTA1	ENST00000934453.1		c.52C>T	p.Gln18*	stop_gained	Exon 1 of 8	ENSP00000604512.1
	VTA1	ENST00000890565.1		c.52C>T	p.Gln18*	stop_gained	Exon 1 of 8	ENSP00000560624.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		5.0
Vest4		0.71
GERP RS		5.6
PromoterAI		-0.0090	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=2/198	disease causing (fs/PTC)

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

hg19: chr6-142468476;