Variant 19-44623748-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001205280.2(IGSF23):c.167G>A(p.Arg56Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,550,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

IGSF23
NM_001205280.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.412

Variant links:

Genes affected

IGSF23 (HGNC:40040): (immunoglobulin superfamily member 23) This gene encodes a protein that has one immunoglobulin (Ig) domain and is a member of the immunoglobulin superfamily. Proteins in this superfamily are usually found on or in cell membranes and act as receptors in immune response pathways. [provided by RefSeq, Nov 2011]

IGSF23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034003258).

BP6

Variant 19-44623748-G-A is Benign according to our data. Variant chr19-44623748-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3108875.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF23	NM_001205280.2 linkuse as main transcript	c.167G>A	p.Arg56Gln	missense_variant	2/5	ENST00000402988.6	NP_001192209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
IGSF23	ENST00000402988.6 linkuse as main transcript	c.167G>A	p.Arg56Gln	missense_variant	2/5	3	NM_001205280.2	ENSP00000385592	P1
IGSF23	ENST00000441389.1 linkuse as main transcript	c.5G>A	p.Arg2Gln	missense_variant	1/3	1		ENSP00000407344
IGSF23	ENST00000428245.5 linkuse as main transcript	c.227G>A	p.Arg76Gln	missense_variant	3/6	5		ENSP00000410629
IGSF23	ENST00000592507.1 linkuse as main transcript	c.170G>A	p.Arg57Gln	missense_variant	2/2	3		ENSP00000465887

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000397

AC:

AN:

151114

Hom.:

AF XY:

0.0000494

AC XY:

AN XY:

80912

show subpopulations

Gnomad AFR exome

AF:

0.000141

Gnomad AMR exome

AF:

0.0000813

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000926

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000114

AC:

AN:

1398782

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

689890

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000463

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.000102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 22, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.26

DANN

Benign

0.38

DEOGEN2

Benign

0.0028

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00032

LIST_S2

Benign

0.40

T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.73

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

0.50

N;.

REVEL

Benign

0.015

Sift

Benign

0.57

T;.

Sift4G

Benign

0.91

T;T

Vest4

0.096

MVP

0.048

ClinPred

0.0070

GERP RS

-2.8

Varity_R

0.023

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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