Genetic Variant IGSF1:p.Val316Val (chrX-131282984-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.27

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF1	NM_001555.5 link	c.948G>A	p.Val316Val	synonymous_variant	Exon 6 of 20	ENST00000361420.8	NP_001546.2	Q8N6C5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGSF1	ENST00000361420.8 link	c.948G>A	p.Val316Val	synonymous_variant	Exon 6 of 20	1	NM_001555.5	ENSP00000355010.3		Q8N6C5-1

Frequencies

GnomAD3 genomes

AF:

0.911

AC:

101170

AN:

111052

Hom.:

32865

Cov.:

AF XY:

0.916

AC XY:

30414

AN XY:

33220

show subpopulations

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

show subpopulations

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.:

AF XY:

0.992

AC XY:

352539

AN XY:

355348

show subpopulations

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.:

AF XY:

0.915

AC XY:

30462

AN XY:

33287

show subpopulations

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:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 02, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over