X-131274153-C-G

Variant summary

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

The NM_001555.5(IGSF1):c.3805G>C(p.Val1269Leu) 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: IGSF1 NM_001555.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

Genes affected

IGSF1 (HGNC:5948): (immunoglobulin superfamily member 1) This gene encodes a member of the immunoglobulin-like domain-containing superfamily. Proteins in this superfamily contain varying numbers of immunoglobulin-like domains and are thought to participate in the regulation of interactions between cells. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 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=0.41935226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF1	NM_001555.5	c.3805G>C	p.Val1269Leu	missense_variant	19/20	ENST00000361420.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF1	ENST00000361420.8	c.3805G>C	p.Val1269Leu	missense_variant	19/20	1	NM_001555.5	P4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jan 04, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	23
Dann	Uncertain	1.0
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.42	T;T;T;T
MetaSVM	Benign	-0.85	T
MutationTaster	Benign	0.68	D;D;N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.69	N;N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		0.17	B;D;.;B
Vest4		0.63
MutPred		0.48		.;Loss of catalytic residue at V1269 (P = 0.0148);.;.;
MVP		0.18
MPC		0.74
ClinPred		0.79	D
GERP RS		4.5
Varity_R		0.21
gMVP		0.83

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-130408127;