Variant 1-116579407-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001007237.3(IGSF3):c.3319C>T(p.Arg1107Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000578 in 1,573,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1107H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

IGSF3
NM_001007237.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.93

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2925042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF3	NM_001007237.3 link	c.3319C>T	p.Arg1107Cys	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.3319C>T	p.Arg1107Cys	missense_variant	10/11	1	NM_001007237.3	ENSP00000358498.4	O75054-1
IGSF3	ENST00000318837.6 link	c.3379C>T	p.Arg1127Cys	missense_variant	10/11	2		ENSP00000321184.6	O75054-2
IGSF3	ENST00000369483.5 link	c.3379C>T	p.Arg1127Cys	missense_variant	11/12	5		ENSP00000358495.1	O75054-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000227

AC:

AN:

220658

Hom.:

AF XY:

0.0000168

AC XY:

AN XY:

118760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000398

Gnomad OTH exome

AF:

0.000189

GnomAD4 exome

AF:

0.0000598

AC:

AN:

1421688

Hom.:

Cov.:

AF XY:

0.0000669

AC XY:

AN XY:

702472

show subpopulations

Gnomad4 AFR exome

AF:

0.0000618

Gnomad4 AMR exome

AF:

0.0000248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000250

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000715

Gnomad4 OTH exome

AF:

0.0000341

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000154

Hom.:

Bravo

AF:

0.0000453

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

The c.3379C>T (p.R1127C) alteration is located in exon 11 (coding exon 10) of the IGSF3 gene. This alteration results from a C to T substitution at nucleotide position 3379, causing the arginine (R) at amino acid position 1127 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

.;T;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

T;T;.

M_CAP

Benign

0.024

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.0

.;L;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.17

Sift

Uncertain

0.0030

D;D;D

Sift4G

Benign

0.076

T;T;T

Polyphen

1.0

.;D;.

Vest4

0.35

MutPred

0.58

.;Loss of disorder (P = 0.0537);.;

MVP

0.21

MPC

1.1

ClinPred

0.28

GERP RS

4.6

Varity_R

0.13

gMVP

0.44

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