Genetic Variant IGSF3:p.Asp1023_Asp1024insAsn (chr1-116579656-C-CGTT) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_001007237.3(IGSF3):c.3069_3070insAAC(p.Asp1023_Asp1024insAsn) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,581,164 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 9 hom. )

Consequence

IGSF3
NM_001007237.3 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.00100

Variant links:

Genes affected

IGSF3 (HGNC:5950): (immunoglobulin superfamily member 3) The protein encoded by this gene is an immunoglobulin-like membrane protein containing several V-type Ig-like domains. A mutation in this gene has been associated with bilateral nasolacrimal duct obstruction (LCDD). [provided by RefSeq, Jun 2016]

IGSF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 1-116579656-C-CGTT is Benign according to our data. Variant chr1-116579656-C-CGTT is described in ClinVar as [Benign]. Clinvar id is 3046067.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGSF3	NM_001007237.3 link	c.3069_3070insAAC	p.Asp1023_Asp1024insAsn	conservative_inframe_insertion	Exon 10 of 11	ENST00000369486.8	NP_001007238.1	O75054-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IGSF3	ENST00000369486.8 link	c.3069_3070insAAC	p.Asp1023_Asp1024insAsn	conservative_inframe_insertion	Exon 10 of 11	1	NM_001007237.3	ENSP00000358498.4	O75054-1
IGSF3	ENST00000318837.6 link	c.3129_3130insAAC	p.Asp1043_Asp1044insAsn	conservative_inframe_insertion	Exon 10 of 11	2		ENSP00000321184.6	O75054-2
IGSF3	ENST00000369483.5 link	c.3129_3130insAAC	p.Asp1043_Asp1044insAsn	conservative_inframe_insertion	Exon 11 of 12	5		ENSP00000358495.1	O75054-2

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

296

AN:

137332

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000200

Gnomad AMI

AF:

0.00794

Gnomad AMR

AF:

0.0000735

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0218

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.000526

GnomAD3 exomes

AF:

0.00268

AC:

585

AN:

218442

Hom.:

AF XY:

0.00263

AC XY:

311

AN XY:

118122

show subpopulations

Gnomad AFR exome

AF:

0.0000660

Gnomad AMR exome

AF:

0.0000625

Gnomad ASJ exome

AF:

0.000110

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0221

Gnomad NFE exome

AF:

0.00196

Gnomad OTH exome

AF:

0.00260

GnomAD4 exome

AF:

0.00136

AC:

1961

AN:

1443696

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

959

AN XY:

718760

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

Gnomad4 AMR exome

AF:

0.0000453

Gnomad4 ASJ exome

AF:

0.000118

Gnomad4 EAS exome

AF:

0.000107

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0185

Gnomad4 NFE exome

AF:

0.000839

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00215

AC:

296

AN:

137468

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

176

AN XY:

66872

show subpopulations

Gnomad4 AFR

AF:

0.000200

Gnomad4 AMR

AF:

0.0000733

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0218

Gnomad4 NFE

AF:

0.00150

Gnomad4 OTH

AF:

0.000520

Alfa

AF:

0.00118

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IGSF3-related disorder

Benign:1

Oct 07, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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