NM_001199799.2:c.486G>C

Variant names:

• chr3-122001758-C-G
• NM_001199799.2:c.486G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_001199799.2(ILDR1):​c.486G>C​(p.Lys162Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Synonymous variant affecting the same amino acid position (i.e. K162K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.872

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]

ACMG classification

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 6 pathogenic changes around while only 2 benign (75%) in NM_001199799.2
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36554855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ILDR1	NM_001199799.2	c.486G>C	p.Lys162Asn	missense_variant	Exon 4 of 8	ENST00000344209.10	NP_001186728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ILDR1	ENST00000344209.10	c.486G>C	p.Lys162Asn	missense_variant	Exon 4 of 8	1	NM_001199799.2	ENSP00000345667.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461380 Hom.: 0 Cov.: 34 AF XY: 0.0000151 AC XY: 11 AN XY: 726982

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: 0.0000153

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

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	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	.;T;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.84	T;.;T
M_CAP	Benign	0.044	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		0.98	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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-121720605;