rs142554264

Variant names:

• chr3-122001758-C-A
• rs142554264
• NM_001199799.2:c.486G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-122001758-C-A
• chr3-122001758-C-T
• chr3-122001758-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: 0.0000027 (0 hom.)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.872
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 42

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36878312).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199799.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILDR1	NM_001199799.2	MANE Select	c.486G>T	p.Lys162Asn	missense	Exon 4 of 8	NP_001186728.1	Q86SU0-1
	ILDR1	NM_175924.4		c.486G>T	p.Lys162Asn	missense	Exon 4 of 7	NP_787120.1	Q86SU0-2
	ILDR1	NM_001199800.2		c.379+3486G>T		intron	N/A	NP_001186729.1	Q86SU0-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILDR1	ENST00000344209.10	TSL:1 MANE Select	c.486G>T	p.Lys162Asn	missense	Exon 4 of 8	ENSP00000345667.5	Q86SU0-1
	ILDR1	ENST00000273691.7	TSL:1	c.486G>T	p.Lys162Asn	missense	Exon 4 of 7	ENSP00000273691.3	Q86SU0-2
	ILDR1	ENST00000393631.5	TSL:1	c.379+3486G>T		intron	N/A	ENSP00000377251.1	Q86SU0-5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251488 AF XY: 0.00000736

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5388

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111982

Other (OTH) AF: 0.0000166 AC: 1 AN: 60354

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.87
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.23
Sift	Uncertain	0.018	D
Sift4G	Benign	0.066	T
Polyphen		0.95	P
Vest4		0.65
MutPred		0.45		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
Mutation Taster		=47/53	disease causing

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

Other links and lift over

dbSNP: rs142554264; hg19: chr3-121720605;