3-118902576-T-A

Position:

• chr3-118902576-T-A

Variant summary

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

The NM_001015887.3(IGSF11):​c.1240A>T​(p.Ile414Phe) variant causes a missense change involving the alteration of a 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: 31)
• Consequence: IGSF11 NM_001015887.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.29

Genes affected

IGSF11 (HGNC:16669): (immunoglobulin superfamily member 11) IGSF11 is an immunoglobulin (Ig) superfamily member that is preferentially expressed in brain and testis. It shares significant homology with coxsackievirus and adenovirus receptor (CXADR; MIM 602621) and endothelial cell-selective adhesion molecule (ESAM).[supplied by OMIM, Apr 2005]

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=0.33631366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF11	NM_001015887.3	c.1240A>T	p.Ile414Phe	missense_variant	7/7	ENST00000393775.7	NP_001015887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGSF11	ENST00000393775.7	c.1240A>T	p.Ile414Phe	missense_variant	7/7	1	NM_001015887.3	ENSP00000377370.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

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

Feb 28, 2024

The c.1240A>T (p.I414F) alteration is located in exon 7 (coding exon 7) of the IGSF11 gene. This alteration results from a A to T substitution at nucleotide position 1240, causing the isoleucine (I) at amino acid position 414 to be replaced by a phenylalanine (F). 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	0.15
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	.;T;.;.;.;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	.;D;D;D;D;D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.34	T;T;T;T;T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.6	.;L;.;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.0	N;N;N;N;N;N
REVEL	Uncertain	0.44
Sift	Uncertain	0.014	D;D;D;D;D;D
Sift4G	Uncertain	0.049	D;T;T;D;D;T
Polyphen		0.49	P;B;B;P;P;B
Vest4		0.43
MutPred		0.42		.;Gain of sheet (P = 0.1539);.;.;.;.;
MVP		0.80
MPC		0.65
ClinPred		0.93	D
GERP RS		5.0
Varity_R		0.22
gMVP		0.55

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: chr3-118621423;