3-121993504-C-G

Variant names:

• chr3-121993504-C-G
• NM_001199799.2:c.1245G>C
• ILDR1 p.Trp415Cys

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001199799.2(ILDR1):​c.1245G>C​(p.Trp415Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.82
• 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: Labcorp Genetics (formerly Invitae), G2P
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1245G>C	p.Trp415Cys	missense	Exon 7 of 8	NP_001186728.1	Q86SU0-1
	ILDR1	NM_175924.4		c.1113G>C	p.Trp371Cys	missense	Exon 6 of 7	NP_787120.1	Q86SU0-2
	ILDR1	NM_001199800.2		c.978G>C	p.Trp326Cys	missense	Exon 5 of 6	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.1245G>C	p.Trp415Cys	missense	Exon 7 of 8	ENSP00000345667.5	Q86SU0-1
	ILDR1	ENST00000273691.7	TSL:1	c.1113G>C	p.Trp371Cys	missense	Exon 6 of 7	ENSP00000273691.3	Q86SU0-2
	ILDR1	ENST00000393631.5	TSL:1	c.978G>C	p.Trp326Cys	missense	Exon 5 of 6	ENSP00000377251.1	Q86SU0-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	0.036	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.8
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.14	T
Varity_R		0.23
gMVP		0.12
Mutation Taster		=82/18	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-121712351;