Genetic Variant NM_001199799.2:c.794C>A (chr3-121993955-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001199799.2(ILDR1):c.794C>A(p.Ser265Tyr) 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. 13/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S265F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ILDR1
NM_001199799.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.90

Publications

2 publications found

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]

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

ILDR1 links:

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ACMG classification

Classification was made for transcript

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=0.34791988).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ILDR1	NM_001199799.2	MANE Select	c.794C>A	p.Ser265Tyr	missense	Exon 7 of 8	NP_001186728.1
ILDR1	NM_175924.4		c.662C>A	p.Ser221Tyr	missense	Exon 6 of 7	NP_787120.1
ILDR1	NM_001199800.2		c.527C>A	p.Ser176Tyr	missense	Exon 5 of 6	NP_001186729.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ILDR1	ENST00000344209.10	TSL:1 MANE Select	c.794C>A	p.Ser265Tyr	missense	Exon 7 of 8	ENSP00000345667.5
ILDR1	ENST00000273691.7	TSL:1	c.662C>A	p.Ser221Tyr	missense	Exon 6 of 7	ENSP00000273691.3
ILDR1	ENST00000393631.5	TSL:1	c.527C>A	p.Ser176Tyr	missense	Exon 5 of 6	ENSP00000377251.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.79

M_CAP

Benign

0.067

MetaRNN

Benign

0.35

MetaSVM

Uncertain

0.18

MutationAssessor

Uncertain

2.6

PhyloP100

1.9

PrimateAI

Benign

0.40

PROVEAN

Benign

0.39

REVEL

Benign

0.17

Sift

Uncertain

0.0010

Sift4G

Benign

1.0

Polyphen

0.99

Vest4

0.39

MutPred

0.26

Gain of catalytic residue at S265 (P = 0.0121)

MVP

0.87

MPC

0.12

ClinPred

0.74

GERP RS

5.0

Varity_R

0.16

gMVP

0.42

Mutation Taster

=65/35

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over