Variant chr2-36767244-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_053276.4(VIT):c.638T>C(p.Ile213Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,441,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

VIT
NM_053276.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

VIT (HGNC:12697): (vitrin) This gene encodes an extracellular matrix (ECM) protein. The protein may be associated with cell adhesion and migration. High levels of expression of the protein in specific parts of the brain suggest its likely role in neural development. [provided by RefSeq, Jun 2016]

VIT links:

LOC124905990 (HGNC:):

LOC124905990 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03351155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIT	NM_053276.4 linkuse as main transcript	c.638T>C	p.Ile213Thr	missense_variant	7/16	ENST00000379242.8	NP_444506.2
LOC124905990	XR_007086283.1 linkuse as main transcript	n.231-2509A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIT	ENST00000379242.8 linkuse as main transcript	c.638T>C	p.Ile213Thr	missense_variant	7/16	2	NM_053276.4	ENSP00000368544	A2	Q6UXI7-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1441464

Hom.:

Cov.:

AF XY:

0.00000419

AC XY:

AN XY:

716250

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000363

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2021

The c.638T>C (p.I213T) alteration is located in exon 7 (coding exon 6) of the VIT gene. This alteration results from a T to C substitution at nucleotide position 638, causing the isoleucine (I) at amino acid position 213 to be replaced by a threonine (T). 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

Benign

0.065

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.5

DANN

Benign

0.27

DEOGEN2

Benign

0.040

.;T;T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.83

T;T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.034

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

N;N;.;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.68

N;N;N;N;N

REVEL

Benign

0.040

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

0.47

T;T;T;T;T

Polyphen

0.0

B;B;.;B;.

Vest4

0.044

MutPred

0.21

Gain of glycosylation at I213 (P = 0.0021);Gain of glycosylation at I213 (P = 0.0021);.;Gain of glycosylation at I213 (P = 0.0021);Gain of glycosylation at I213 (P = 0.0021);

MVP

0.41

MPC

0.027

ClinPred

0.042

GERP RS

1.5

Varity_R

0.033

gMVP

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over