X-131282984-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001555.5(IGSF1):c.948G>A(p.Val316=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (32859 hom., 30462 hem., cov: 23)
  • Exomes 𝑓: 0.99 (359872 hom. 352539 hem.)
  • Failed GnomAD Quality Control
• Consequence: IGSF1 NM_001555.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.27

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 Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant X-131282984-C-T is Benign according to our data. Variant chrX-131282984-C-T is described in ClinVar as [Benign]. Clinvar id is 257593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-131282984-C-T is described in Lovd as [Likely_benign]. Variant chrX-131282984-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.27 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 32865 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGSF1	NM_001555.5	c.948G>A	p.Val316=	synonymous_variant	6/20	ENST00000361420.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IGSF1	ENST00000361420.8	c.948G>A	p.Val316=	synonymous_variant	6/20	1	NM_001555.5	P4

Frequencies

GnomAD3 genomes AF: 0.911 AC: 101170 AN: 111052 Hom.: 32865 Cov.: 23 AF XY: 0.916 AC XY: 30414 AN XY: 33220

Gnomad AFR AF: 0.695

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.926

GnomAD3 exomes AF: 0.974 AC: 176326 AN: 181040 Hom.: 54463 AF XY: 0.982 AC XY: 64883 AN XY: 66066

Gnomad AFR exome AF: 0.685

Gnomad AMR exome AF: 0.985

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.986

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.990 AC: 1077977 AN: 1088488 Hom.: 359872 Cov.: 28 AF XY: 0.992 AC XY: 352539 AN XY: 355348

Gnomad4 AFR exome AF: 0.689

Gnomad4 AMR exome AF: 0.982

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.977

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.911 AC: 101208 AN: 111109 Hom.: 32859 Cov.: 23 AF XY: 0.915 AC XY: 30462 AN XY: 33287

Gnomad4 AFR AF: 0.695

Gnomad4 AMR AF: 0.958

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.927

Alfa AF: 0.968 Hom.: 16196

Bravo AF: 0.897

EpiCase AF: 0.999

EpiControl AF: 0.998

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

X-linked central congenital hypothyroidism with late-onset testicular enlargement Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 02, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	10
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs5932877; hg19: chrX-130416958;