rs1128617

Positions:

• chrX-131281844-T-A
• chrX-131281844-T-C
• chrX-131281844-T-G

Variant summary

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

The NM_001555.5(IGSF1):​c.1347A>T​(p.Glu449Asp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E449E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: IGSF1 NM_001555.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14622006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF1	NM_001555.5	c.1347A>T	p.Glu449Asp	missense_variant	8/20	ENST00000361420.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF1	ENST00000361420.8	c.1347A>T	p.Glu449Asp	missense_variant	8/20	1	NM_001555.5	P4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.76	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.99	P;P;P;P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.50	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.20	T;T;D;T
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.98	D;D;.;D
Vest4		0.10
MutPred		0.28		.;Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;
MVP		0.23
MPC		0.71
ClinPred		0.87	D
GERP RS		3.2
Varity_R		0.13
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1128617; hg19: chrX-130415818;