10-112464560-A-C

Variant names:

• chr10-112464560-A-C
• NM_145206.4:c.167A>C

Variant summary

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

The NM_145206.4(VTI1A):​c.167A>C​(p.Asp56Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: VTI1A NM_145206.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.68
• Publications: 0 publications found

Genes affected

VTI1A (HGNC:17792): (vesicle transport through interaction with t-SNAREs 1A) The protein encoded by this gene is a member of the family of soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptors (SNAREs) that function in intracellular trafficking. This family member is involved in vesicular transport between endosomes and the trans-Golgi network. It is a vesicle-associated SNARE (v-SNARE) that interacts with target membrane SNAREs (t-SNAREs). Polymorphisms in this gene have been associated with binocular function, and also with susceptibility to colorectal and lung cancers. A recurrent rearrangement has been found between this gene and the transcription factor 7-like 2 (TCF7L2) gene in colorectal cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
VTI1A	NM_145206.4	c.167A>C	p.Asp56Ala	missense_variant	Exon 3 of 8	ENST00000393077.3	NP_660207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTI1A	ENST00000393077.3	c.167A>C	p.Asp56Ala	missense_variant	Exon 3 of 8	2	NM_145206.4	ENSP00000376792.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.167A>C (p.D56A) alteration is located in exon 3 (coding exon 3) of the VTI1A gene. This alteration results from a A to C substitution at nucleotide position 167, causing the aspartic acid (D) at amino acid position 56 to be replaced by an alanine (A). 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	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.7	M;M
PhyloP100		8.7
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.63
Sift	Benign	0.076	T;D
Sift4G	Benign	0.074	T;T
Polyphen		0.53	.;P
Vest4		0.56
MutPred		0.56		Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.45
MPC		0.38
ClinPred		0.96	D
GERP RS		5.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.35
gMVP		0.57
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr10-114224319;