3-121993167-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001199799.2(ILDR1):ā€‹c.1582A>Gā€‹(p.Ser528Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

ILDR1
NM_001199799.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ILDR1NM_001199799.2 linkuse as main transcriptc.1582A>G p.Ser528Gly missense_variant 7/8 ENST00000344209.10 NP_001186728.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ILDR1ENST00000344209.10 linkuse as main transcriptc.1582A>G p.Ser528Gly missense_variant 7/81 NM_001199799.2 ENSP00000345667 P2Q86SU0-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1452960
Hom.:
0
Cov.:
30
AF XY:
0.00000139
AC XY:
1
AN XY:
721844
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:
9.03e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000378

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 submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineApr 28, 2015Variant classified as Uncertain Significance - Favor Benign. The p.Ser528Gly var iant in ILDR1 has not been previously reported in individuals with hearing loss. Data from large population studies are insufficient to assess the frequency of this variant. Serine (Ser) at position 528 is not conserved in mammals or evolut ionarily distant species and 2 avian species (chicken and turkey) carry a glycin e (Gly) at the position, raising the possibility that this change may be tolerat ed. Additional computational prediction tools suggest that the variant may not i mpact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Ser528Gly va riant is uncertain, the lack of conservation suggests that it is more likely to be benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.079
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0028
.;T;T;.
Eigen
Benign
-0.032
Eigen_PC
Benign
0.13
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.66
T;.;T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
1.7
.;L;L;.
MutationTaster
Benign
0.97
N;N;N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-1.1
N;N;.;N
REVEL
Benign
0.090
Sift
Benign
0.29
T;T;.;T
Sift4G
Benign
0.52
T;T;.;T
Polyphen
0.50
P;B;B;P
Vest4
0.28
MutPred
0.18
.;Loss of phosphorylation at S528 (P = 0.0031);Loss of phosphorylation at S528 (P = 0.0031);.;
MVP
0.74
MPC
0.038
ClinPred
0.40
T
GERP RS
5.8
Varity_R
0.14
gMVP
0.073

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.25
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.25
Position offset: -17

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: rs727503095; hg19: chr3-121712014; API