dbSNP rs1427391500: VTI1A:p.Arg28Gln (chr10-112447456-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145206.4(VTI1A):c.83G>A(p.Arg28Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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. R28P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

VTI1A
NM_145206.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.92

Publications

0 publications found

Variant links:

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]

VTI1A links:

ZDHHC6 (HGNC:19160): (zinc finger DHHC-type palmitoyltransferase 6) Enables palmitoyltransferase activity. Involved in positive regulation of mitochondrial fusion and protein palmitoylation. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC6 links:

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ACMG classification

Classification was made for transcript

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=0.1348241).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTI1A	NM_145206.4 link	c.83G>A	p.Arg28Gln	missense_variant	Exon 1 of 8	ENST00000393077.3	NP_660207.2	Q96AJ9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTI1A	ENST00000393077.3 link	c.83G>A	p.Arg28Gln	missense_variant	Exon 1 of 8	2	NM_145206.4	ENSP00000376792.2		Q96AJ9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250206

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461110

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726796

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5446

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111886

Other (OTH)

AF:

0.00

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.070

.;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.0014

FATHMM_MKL

Benign

0.23

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.0059

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.27

N;N

PhyloP100

5.9

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.089

Sift

Benign

0.72

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.0040

.;B

Vest4

0.24

MutPred

0.39

Loss of loop (P = 0.0073);Loss of loop (P = 0.0073);

MVP

0.65

MPC

0.20

ClinPred

0.53

GERP RS

3.8

PromoterAI

-0.023

Neutral

(source)

Varity_R

0.12

gMVP

0.23

Mutation Taster

=75/25

polymorphism

(source)

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

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rs1427391500

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over