rs5932877

Variant names:

• chrX-131282984-C-T
• rs5932877
• NM_001555.5:c.948G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-131282984-C-T
• chrX-131282984-C-A
• chrX-131282984-C-G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001555.5(IGSF1):​c.948G>A​(p.Val316Val) 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:6
• Conservation: PhyloP100: -1.27
• Publications: 13 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ENSG00000287806 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 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 VariationId is 257593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.27 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001555.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF1	NM_001555.5	MANE Select	c.948G>A	p.Val316Val	synonymous	Exon 6 of 20	NP_001546.2
	IGSF1	NM_001170961.2		c.948G>A	p.Val316Val	synonymous	Exon 6 of 20	NP_001164432.1	Q8N6C5-4
	IGSF1	NM_001438811.1		c.948G>A	p.Val316Val	synonymous	Exon 7 of 21	NP_001425740.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGSF1	ENST00000361420.8	TSL:1 MANE Select	c.948G>A	p.Val316Val	synonymous	Exon 6 of 20	ENSP00000355010.3	Q8N6C5-1
	IGSF1	ENST00000370903.8	TSL:1	c.948G>A	p.Val316Val	synonymous	Exon 6 of 20	ENSP00000359940.3	Q8N6C5-4
	IGSF1	ENST00000370910.5	TSL:1	c.921G>A	p.Val307Val	synonymous	Exon 5 of 19	ENSP00000359947.1	Q8N6C5-2

Frequencies

GnomAD3 genomes AF: 0.911 AC: 101170 AN: 111052 Hom.: 32865 Cov.: 23

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

GnomAD2 exomes AF: 0.974 AC: 176326 AN: 181040 AF XY: 0.982

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 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

African (AFR) AF: 0.689 AC: 17992 AN: 26127

American (AMR) AF: 0.982 AC: 34455 AN: 35078

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 19280 AN: 19281

East Asian (EAS) AF: 1.00 AC: 30130 AN: 30130

South Asian (SAS) AF: 1.00 AC: 53837 AN: 53863

European-Finnish (FIN) AF: 1.00 AC: 40513 AN: 40513

Middle Eastern (MID) AF: 0.985 AC: 4052 AN: 4114

European-Non Finnish (NFE) AF: 0.999 AC: 833014 AN: 833635

Other (OTH) AF: 0.977 AC: 44704 AN: 45747

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

African (AFR) AF: 0.695 AC: 21204 AN: 30496

American (AMR) AF: 0.958 AC: 10011 AN: 10448

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2637 AN: 2637

East Asian (EAS) AF: 1.00 AC: 3546 AN: 3546

South Asian (SAS) AF: 1.00 AC: 2547 AN: 2548

European-Finnish (FIN) AF: 1.00 AC: 5948 AN: 5948

Middle Eastern (MID) AF: 0.977 AC: 212 AN: 217

European-Non Finnish (NFE) AF: 0.999 AC: 53022 AN: 53078

Other (OTH) AF: 0.927 AC: 1396 AN: 1506

Alfa AF: 0.968 Hom.: 16196

Bravo AF: 0.897

EpiCase AF: 0.999

EpiControl AF: 0.998

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	X-linked central congenital hypothyroidism with late-onset testicular enlargement (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Benign	0.78
PhyloP100		-1.3
PromoterAI		0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5932877; hg19: chrX-130416958; COSMIC: COSV108209550; COSMIC: COSV108209550;