rs1556181091

Variant names:

• chrX-131278026-TCCTTATACAGAGCAAACCCCATGCCTG-T
• rs1556181091
• NM_001555.5:c.2123_2149delCAGGCATGGGGTTTGCTCTGTATAAGG

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_001555.5(IGSF1):​c.2123_2149delCAGGCATGGGGTTTGCTCTGTATAAGG​(p.Ala708_Lys716del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: IGSF1 NM_001555.5 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.08

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001555.5.
• PP5: Variant X-131278026-TCCTTATACAGAGCAAACCCCATGCCTG-T is Pathogenic according to our data. Variant chrX-131278026-TCCTTATACAGAGCAAACCCCATGCCTG-T is described in ClinVar as [Pathogenic]. Clinvar id is 39849.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-131278026-TCCTTATACAGAGCAAACCCCATGCCTG-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF1	NM_001555.5	c.2123_2149delCAGGCATGGGGTTTGCTCTGTATAAGG	p.Ala708_Lys716del	disruptive_inframe_deletion	Exon 13 of 20	ENST00000361420.8	NP_001546.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF1	ENST00000361420.8	c.2123_2149delCAGGCATGGGGTTTGCTCTGTATAAGG	p.Ala708_Lys716del	disruptive_inframe_deletion	Exon 13 of 20	1	NM_001555.5	ENSP00000355010.3

Frequencies

GnomAD3 genomes Cov.: 22

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

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

Dec 01, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1556181091; hg19: chrX-130412000;