X-66025082-A-G

Position:

• chrX-66025082-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007268.3(VSIG4):​c.883T>C​(p.Cys295Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: VSIG4 NM_007268.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.775

Genes affected

VSIG4 (HGNC:17032): (V-set and immunoglobulin domain containing 4) This gene encodes a v-set and immunoglobulin-domain containing protein that is structurally related to the B7 family of immune regulatory proteins. The encoded protein may be a negative regulator of T-cell responses. This protein is also a receptor for the complement component 3 fragments C3b and iC3b. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31878057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VSIG4	NM_007268.3	c.883T>C	p.Cys295Arg	missense_variant	6/8	ENST00000374737.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VSIG4	ENST00000374737.9	c.883T>C	p.Cys295Arg	missense_variant	6/8	1	NM_007268.3	P2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

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

May 02, 2024

The c.883T>C (p.C295R) alteration is located in exon 6 (coding exon 6) of the VSIG4 gene. This alteration results from a T to C substitution at nucleotide position 883, causing the cysteine (C) at amino acid position 295 to be replaced by an arginine (R). 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	Pathogenic	0.85
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.28	T;.;.
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.45
MutPred		0.56		Gain of MoRF binding (P = 0.027);Gain of MoRF binding (P = 0.027);.;
MVP		0.081
MPC		0.015
ClinPred		0.48	T
GERP RS		3.0
Varity_R		0.63
gMVP		0.45

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: chrX-65244924;