chr2-36743122-T-A

Position:

• chr2-36743122-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_053276.4(VIT):​c.141T>A​(p.Asp47Glu) variant causes a missense change involving the alteration of a non-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: 32)
• Consequence: VIT NM_053276.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66

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]

LOC124905990 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIT	NM_053276.4	c.141T>A	p.Asp47Glu	missense_variant	4/16	ENST00000379242.8	NP_444506.2
LOC124905990	XR_007086283.1	n.334+21510A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIT	ENST00000379242.8	c.141T>A	p.Asp47Glu	missense_variant	4/16	2	NM_053276.4	ENSP00000368544	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.141T>A (p.D47E) alteration is located in exon 4 (coding exon 3) of the VIT gene. This alteration results from a T to A substitution at nucleotide position 141, causing the aspartic acid (D) at amino acid position 47 to be replaced by a glutamic acid (E). 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	0.16
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	.;T;.;T;.;.
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;D;D;D;D;D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.47	T;T;T;T;T;T
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.4	L;L;L;.;L;L
MutationTaster	Benign	0.97	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.6	N;N;N;N;N;N
REVEL	Pathogenic	0.71
Sift	Benign	0.048	D;T;T;T;T;T
Sift4G	Uncertain	0.046	D;T;T;T;T;T
Polyphen		1.0	D;D;D;.;D;.
Vest4		0.41
MutPred		0.67		Gain of methylation at K49 (P = 0.0724);Gain of methylation at K49 (P = 0.0724);Gain of methylation at K49 (P = 0.0724);.;Gain of methylation at K49 (P = 0.0724);Gain of methylation at K49 (P = 0.0724);
MVP		0.69
MPC		0.11
ClinPred		0.98	D
GERP RS		3.6
Varity_R		0.16
gMVP		0.43

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: chr2-36970265;