Variant 1-116579663-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001007237.3(IGSF3):c.3063C>G(p.Asp1021Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 1,564,050 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0052 ( 10 hom., cov: 28)

Exomes 𝑓: 0.0037 ( 18 hom. )

Consequence

IGSF3
NM_001007237.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.34

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007328391).

BP6

Variant 1-116579663-G-C is Benign according to our data. Variant chr1-116579663-G-C is described in ClinVar as [Benign]. Clinvar id is 3041771.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00525 (790/150494) while in subpopulation AMR AF= 0.0204 (309/15150). AF 95% confidence interval is 0.0185. There are 10 homozygotes in gnomad4. There are 465 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF3	NM_001007237.3 link	c.3063C>G	p.Asp1021Glu	missense_variant	10/11	ENST00000369486.8	NP_001007238.1	O75054-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGSF3	ENST00000369486.8 link	c.3063C>G	p.Asp1021Glu	missense_variant	10/11	1	NM_001007237.3	ENSP00000358498.4	O75054-1
IGSF3	ENST00000318837.6 link	c.3123C>G	p.Asp1041Glu	missense_variant	10/11	2		ENSP00000321184.6	O75054-2
IGSF3	ENST00000369483.5 link	c.3123C>G	p.Asp1041Glu	missense_variant	11/12	5		ENSP00000358495.1	O75054-2

Frequencies

GnomAD3 genomes

AF:

0.00525

AC:

790

AN:

150376

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000684

Gnomad AMI

AF:

0.00680

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00484

Gnomad FIN

AF:

0.0191

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.00309

Gnomad OTH

AF:

0.00873

GnomAD3 exomes

AF:

0.00726

AC:

1555

AN:

214242

Hom.:

AF XY:

0.00679

AC XY:

785

AN XY:

115596

show subpopulations

Gnomad AFR exome

AF:

0.000411

Gnomad AMR exome

AF:

0.0220

Gnomad ASJ exome

AF:

0.000338

Gnomad EAS exome

AF:

0.000171

Gnomad SAS exome

AF:

0.00333

Gnomad FIN exome

AF:

0.0211

Gnomad NFE exome

AF:

0.00385

Gnomad OTH exome

AF:

0.00604

GnomAD4 exome

AF:

0.00368

AC:

5198

AN:

1413556

Hom.:

Cov.:

AF XY:

0.00362

AC XY:

2542

AN XY:

702966

show subpopulations

Gnomad4 AFR exome

AF:

0.000428

Gnomad4 AMR exome

AF:

0.0211

Gnomad4 ASJ exome

AF:

0.000236

Gnomad4 EAS exome

AF:

0.000228

Gnomad4 SAS exome

AF:

0.00340

Gnomad4 FIN exome

AF:

0.0193

Gnomad4 NFE exome

AF:

0.00260

Gnomad4 OTH exome

AF:

0.00329

GnomAD4 genome

AF:

0.00525

AC:

790

AN:

150494

Hom.:

Cov.:

AF XY:

0.00633

AC XY:

465

AN XY:

73486

show subpopulations

Gnomad4 AFR

AF:

0.000682

Gnomad4 AMR

AF:

0.0204

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00484

Gnomad4 FIN

AF:

0.0191

Gnomad4 NFE

AF:

0.00309

Gnomad4 OTH

AF:

0.00864

Alfa

AF:

0.00188

Hom.:

ExAC

AF:

0.00583

AC:

706

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

IGSF3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 26, 2019

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

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.023

DANN

Benign

0.18

DEOGEN2

Benign

0.013

.;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.19

T;T;.

MetaRNN

Benign

0.0073

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.17

.;N;.

PrimateAI

Benign

0.33

PROVEAN

Benign

0.24

N;N;N

REVEL

Benign

0.015

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.78

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.077

MutPred

0.27

.;Loss of stability (P = 0.2926);.;

MVP

0.068

MPC

0.52

ClinPred

0.0017

GERP RS

0.33

Varity_R

0.046

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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