chr2-36716386-C-T

Position:

• chr2-36716386-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_053276.4(VIT):​c.16C>T​(p.Leu6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VIT NM_053276.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.38

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21817228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIT	NM_053276.4	c.16C>T	p.Leu6Phe	missense_variant	2/16	ENST00000379242.8	NP_444506.2
LOC124905990	XR_007086283.1	n.335-26726G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIT	ENST00000379242.8	c.16C>T	p.Leu6Phe	missense_variant	2/16	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

Jan 03, 2022

The c.16C>T (p.L6F) alteration is located in exon 2 (coding exon 1) of the VIT gene. This alteration results from a C to T substitution at nucleotide position 16, causing the leucine (L) at amino acid position 6 to be replaced by a phenylalanine (F). 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	0.074
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	.;T;.;T;.;.
Eigen	Benign	0.058
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.84	T;T;T;T;T;T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.22	T;T;T;T;T;T
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.1	M;M;M;.;M;M
MutationTaster	Benign	1.0	D;N;N;N;N;N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.18	N;N;N;N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.029	D;D;D;T;D;D
Sift4G	Benign	0.072	T;T;T;T;T;T
Polyphen		0.69	P;.;.;.;.;.
Vest4		0.25
MutPred		0.33		Gain of catalytic residue at L6 (P = 0.0193);Gain of catalytic residue at L6 (P = 0.0193);Gain of catalytic residue at L6 (P = 0.0193);Gain of catalytic residue at L6 (P = 0.0193);Gain of catalytic residue at L6 (P = 0.0193);Gain of catalytic residue at L6 (P = 0.0193);
MVP		0.90
MPC		0.064
ClinPred		0.77	D
GERP RS		3.1
Varity_R		0.068
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs1666137789; hg19: chr2-36943529; COSMIC: COSV64897903;