chrX-131546956-C-T

Variant names:

• chrX-131546956-C-T
• rs10521769
• ENST00000370904.6:c.-913+31712G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000370904.6(IGSF1):​c.-913+31712G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.59 (13895 hom., 18947 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: IGSF1 ENST00000370904.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• X-linked central congenital hypothyroidism with late-onset testicular enlargement

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF1	ENST00000370904.6	c.-913+31712G>A		intron_variant	Intron 1 of 26	2		ENSP00000359941.1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 65191 AN: 109687 Hom.: 13900 Cov.: 22

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.590

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.594 AC: 65217 AN: 109743 Hom.: 13895 Cov.: 22 AF XY: 0.591 AC XY: 18947 AN XY: 32033

African (AFR) AF: 0.547 AC: 16468 AN: 30131

American (AMR) AF: 0.520 AC: 5361 AN: 10308

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 1798 AN: 2625

East Asian (EAS) AF: 0.648 AC: 2242 AN: 3458

South Asian (SAS) AF: 0.736 AC: 1838 AN: 2497

European-Finnish (FIN) AF: 0.624 AC: 3566 AN: 5713

Middle Eastern (MID) AF: 0.748 AC: 160 AN: 214

European-Non Finnish (NFE) AF: 0.618 AC: 32528 AN: 52633

Other (OTH) AF: 0.593 AC: 883 AN: 1490

Alfa AF: 0.606 Hom.: 84389

Bravo AF: 0.583

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.089
DANN	Benign	0.67
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs10521769; hg19: chrX-130680930;