X-131274681-G-C

Position:

• chrX-131274681-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_001555.5(IGSF1):​c.3669C>G​(p.Asn1223Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.606

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 4 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity IGSF1_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF1	NM_001555.5	c.3669C>G	p.Asn1223Lys	missense_variant	18/20	ENST00000361420.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF1	ENST00000361420.8	c.3669C>G	p.Asn1223Lys	missense_variant	18/20	1	NM_001555.5	P4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

X-linked central congenital hypothyroidism with late-onset testicular enlargement Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Mar 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	.;T;.;.
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.79	.;T;T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.98	.;L;.;.
MutationTaster	Benign	0.76	D;D;D;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.91	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.46	P;D;.;P
Vest4		0.64
MutPred		0.53		.;Gain of methylation at N1223 (P = 0.0124);.;.;
MVP		0.093
MPC		0.80
ClinPred		0.31	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.75

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-130408655;