rs387907015

Variant names:

• chr3-121993614-C-A
• rs387907015
• NM_001199799.2:c.1135G>T
• ILDR1 p.Glu379*

Your query was ambiguous. Multiple possible variants found:

• chr3-121993614-C-A
• chr3-121993614-C-G
• chr3-121993614-C-T

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001199799.2(ILDR1):​c.1135G>T​(p.Glu379*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ILDR1 NM_001199799.2 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.71
• Publications: 6 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: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-121993614-C-A is Pathogenic according to our data. Variant chr3-121993614-C-A is described in ClinVar as Pathogenic. ClinVar VariationId is 30796.Status of the report is no_assertion_criteria_provided, 0 stars.

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.1135G>T	p.Glu379*	stop_gained	Exon 7 of 8	NP_001186728.1	Q86SU0-1
	ILDR1	NM_175924.4		c.1003G>T	p.Glu335*	stop_gained	Exon 6 of 7	NP_787120.1	Q86SU0-2
	ILDR1	NM_001199800.2		c.868G>T	p.Glu290*	stop_gained	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.1135G>T	p.Glu379*	stop_gained	Exon 7 of 8	ENSP00000345667.5	Q86SU0-1
	ILDR1	ENST00000273691.7	TSL:1	c.1003G>T	p.Glu335*	stop_gained	Exon 6 of 7	ENSP00000273691.3	Q86SU0-2
	ILDR1	ENST00000393631.5	TSL:1	c.868G>T	p.Glu290*	stop_gained	Exon 5 of 6	ENSP00000377251.1	Q86SU0-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Autosomal recessive nonsyndromic hearing loss 42 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	35
DANN	Uncertain	1.0
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Benign	0.41	N
PhyloP100		1.7
Mutation Taster		=0/200	disease causing (ClinVar)

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

dbSNP: rs387907015;

hg19: chr3-121712461;