rs142554264

Variant summary

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

The NM_001199799.2(ILDR1):​c.486G>T​(p.Lys162Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ILDR1
NM_001199799.2 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.872
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]

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=0.36878312).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ILDR1NM_001199799.2 linkc.486G>T p.Lys162Asn missense_variant Exon 4 of 8 ENST00000344209.10 NP_001186728.1 Q86SU0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ILDR1ENST00000344209.10 linkc.486G>T p.Lys162Asn missense_variant Exon 4 of 8 1 NM_001199799.2 ENSP00000345667.5 Q86SU0-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251488
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135918
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461380
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
726982
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 28, 2013
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The Lys162Asn variant in ILDR1 has not been reported in individuals with hearing loss or in large population studies. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Lys162Asn variant may impact the protein, though this information is not predict ive enough to determine pathogenicity. In summary, additional information is nee ded to fully assess the clinical significance of the Lys162Asn variant. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Benign
-0.048
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.053
.;T;T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.35
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.84
T;.;T
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.37
T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
1.7
L;L;L
PrimateAI
Uncertain
0.77
T
PROVEAN
Uncertain
-2.5
D;D;.
REVEL
Benign
0.23
Sift
Uncertain
0.018
D;D;.
Sift4G
Benign
0.066
T;D;.
Polyphen
0.95
P;P;P
Vest4
0.65
MutPred
0.45
Loss of methylation at K162 (P = 0.0096);Loss of methylation at K162 (P = 0.0096);Loss of methylation at K162 (P = 0.0096);
MVP
0.62
MPC
0.30
ClinPred
0.96
D
GERP RS
-1.2
Varity_R
0.47
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.

Other links and lift over

dbSNP: rs142554264; hg19: chr3-121720605; API