Variant rs587777040 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_001135022.2(ELMOD3):c.794T>C(p.Leu265Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ELMOD3
NM_001135022.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.90

Variant links:

Genes affected

ELMOD3 (HGNC:26158): (ELMO domain containing 3) This gene encodes a member of the engulfment and cell motility family of GTPase-activating proteins that regulate Arf GTPase proteins. Members of this family are defined by a conserved engulfment and cell motility domain. In rat cochlea, the encoded protein is found in stereocilia, kinocilia and cuticular plate of developing hair cells suggesting a function for this protein in cochlear sensory cells. An allelic variant of this family has been associated with autosomal recessive nonsyndromic deafness-88 in humans. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

ELMOD3 links:

ELMOD3 (HGNC:):

ELMOD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.941

PP5

Variant 2-85389806-T-C is Pathogenic according to our data. Variant chr2-85389806-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 65464.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-85389806-T-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELMOD3	NM_001135022.2 linkuse as main transcript	c.794T>C	p.Leu265Ser	missense_variant	12/14	ENST00000409013.8	NP_001128494.1	Q96FG2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELMOD3	ENST00000409013.8 linkuse as main transcript	c.794T>C	p.Leu265Ser	missense_variant	12/14	1	NM_001135022.2	ENSP00000387139.3		Q96FG2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251362

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135846

show subpopulations

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 SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461794

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 88

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

T;T;T;.;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

.;.;.;D;D

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.94

D;D;D;D;D

MetaSVM

Benign

-0.40

MutationAssessor

Pathogenic

3.6

H;H;H;H;H

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-5.0

D;D;D;D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

D;D;D;D;D

Sift4G

Uncertain

0.010

D;D;D;D;D

Polyphen

1.0

D;D;D;D;D

Vest4

0.97

MutPred

0.78

Gain of disorder (P = 0.0079);Gain of disorder (P = 0.0079);Gain of disorder (P = 0.0079);Gain of disorder (P = 0.0079);Gain of disorder (P = 0.0079);

MVP

0.51

MPC

0.82

ClinPred

1.0

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.89

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over