chrX-131273888-C-T

Position:

• chrX-131273888-C-T

Variant summary

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

The NM_001555.5(IGSF1):​c.3919G>A​(p.Glu1307Lys) 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.

• Frequency: Genomes: not found (cov: 22)
• Consequence: IGSF1 NM_001555.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03

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]

IGSF1 (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=0.21207908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF1	NM_001555.5	c.3919G>A	p.Glu1307Lys	missense_variant	20/20	ENST00000361420.8	NP_001546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF1	ENST00000361420.8	c.3919G>A	p.Glu1307Lys	missense_variant	20/20	1	NM_001555.5	ENSP00000355010.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 27, 2024

The c.3934G>A (p.E1312K) alteration is located in exon 20 (coding exon 19) of the IGSF1 gene. This alteration results from a G to A substitution at nucleotide position 3934, causing the glutamic acid (E) at amino acid position 1312 to be replaced by a lysine (K). 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	0.22
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.037	.;T;.;.
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.89	.;D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.81	.;L;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.39	N;N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0050	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.22	B;P;.;B
Vest4		0.30
MutPred		0.47		.;Gain of methylation at E1307 (P = 5e-04);.;.;
MVP		0.10
MPC		0.55
ClinPred		0.63	D
GERP RS		4.1
Varity_R		0.29
gMVP		0.79

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-130407862;