NM_001199799.2:c.660C>A

Variant names:

• chr3-121994300-G-T
• rs759965447
• NM_001199799.2:c.660C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001199799.2(ILDR1):​c.660C>A​(p.His220Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H220H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ILDR1 NM_001199799.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623
• 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, PanelApp Australia
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21905509).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILDR1	NM_001199799.2	MANE Select	c.660C>A	p.His220Gln	missense	Exon 6 of 8	NP_001186728.1
	ILDR1	NM_001199800.2		c.393C>A	p.His131Gln	missense	Exon 4 of 6	NP_001186729.1
	ILDR1	NM_175924.4		c.647-330C>A		intron	N/A	NP_787120.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ILDR1	ENST00000344209.10	TSL:1 MANE Select	c.660C>A	p.His220Gln	missense	Exon 6 of 8	ENSP00000345667.5
	ILDR1	ENST00000393631.5	TSL:1	c.393C>A	p.His131Gln	missense	Exon 4 of 6	ENSP00000377251.1
	ILDR1	ENST00000273691.7	TSL:1	c.647-330C>A		intron	N/A	ENSP00000273691.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.097
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.62
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.32
Sift	Benign	0.039	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.022	B
Vest4		0.43
MutPred		0.40		Gain of ubiquitination at K224 (P = 0.071)
MVP		0.82
MPC		0.040
ClinPred		0.88	D
GERP RS		2.5
Varity_R		0.35
gMVP		0.64
Mutation Taster		=58/42	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

Other links and lift over

dbSNP: rs759965447; hg19: chr3-121713147;