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: Not reported in ClinVar
• 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

Not reported in ClinVar

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;