3-122005271-G-A

Position:

chr3-122005271-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_001199799.2(ILDR1):c.352C>T(p.Arg118Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000454 in 1,562,362 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000047 ( 1 hom. )

Consequence

ILDR1
NM_001199799.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 2.20

Variant links:

Genes affected

ILDR1 (HGNC:28741): (immunoglobulin like domain containing receptor 1) This gene encodes a protein that contains an immunoglobulin-like domain. The encoded protein may function as a multimeric receptor at the cell surface. The expression of this gene may be a diagnostic marker for cancer progression. Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

ILDR1 links:

ILDR1 (HGNC:):

ILDR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a domain Ig-like V-type (size 138) in uniprot entity ILDR1_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_001199799.2

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28080943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILDR1	NM_001199799.2 linkuse as main transcript	c.352C>T	p.Arg118Trp	missense_variant	3/8	ENST00000344209.10	NP_001186728.1	Q86SU0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILDR1	ENST00000344209.10 linkuse as main transcript	c.352C>T	p.Arg118Trp	missense_variant	3/8	1	NM_001199799.2	ENSP00000345667.5		Q86SU0-1

Frequencies

GnomAD3 genomes

AF:

0.0000272

AC:

AN:

146818

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000206

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:

0.000490

GnomAD3 exomes

AF:

0.000199

AC:

AN:

251062

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00145

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000473

AC:

AN:

1415544

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

703818

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00144

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.24e-7

Gnomad4 OTH exome

AF:

0.0000525

GnomAD4 genome

AF:

0.0000272

AC:

AN:

146818

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71202

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000206

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:

0.000490

Alfa

AF:

0.0000590

Hom.:

Bravo

AF:

0.0000945

ExAC

AF:

0.000148

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:3

Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 23, 2022	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 118 of the ILDR1 protein (p.Arg118Trp). This variant is present in population databases (rs774128939, gnomAD 0.2%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with ILDR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 289899). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 30, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Mar 21, 2023	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 16, 2017

The p.Arg118Trp variant in ILDR1 has not been previously reported in individuals with hearing loss, but has been reported in ClinVar (Variation ID# 289899) as o f uncertain clinical significance. This variant has been identified in 0.2% (53/ 33566) of Latino chromosomes including one homozygote by the Genome Aggregation Database (gnomAD, http://gnomAD.broadinstitute.org; dbSNP rs774128939). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conse rvation analysis suggest that the p.Arg118Trp variant may impact the protein, th ough this information is not predictive enough to determine pathogenicity. In su mmary, the clinical significance of the p.Arg118Trp variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

.;T;T;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.97

D;.;D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.0

M;M;M;M

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-6.1

D;D;D;D

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;.;D

Polyphen

1.0

D;D;D;D

Vest4

0.73

MutPred

0.43

Gain of ubiquitination at K121 (P = 0.0369);Gain of ubiquitination at K121 (P = 0.0369);Gain of ubiquitination at K121 (P = 0.0369);Gain of ubiquitination at K121 (P = 0.0369);

MVP

0.68

MPC

0.29

ClinPred

0.35

GERP RS

3.8

Varity_R

0.76

gMVP

0.69

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