chr2-85363163-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001135022.2(ELMOD3):c.196C>T(p.Arg66Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 1,601,340 control chromosomes in the GnomAD database, including 1,544 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.062 ( 563 hom., cov: 32)

Exomes 𝑓: 0.028 ( 981 hom. )

Consequence

ELMOD3
NM_001135022.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0310

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001386553).

BP6

Variant 2-85363163-C-T is Benign according to our data. Variant chr2-85363163-C-T is described in ClinVar as [Benign]. Clinvar id is 508136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-85363163-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMOD3	NM_001135022.2 link	c.196C>T	p.Arg66Cys	missense_variant	Exon 6 of 14	ENST00000409013.8	NP_001128494.1	Q96FG2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELMOD3	ENST00000409013.8 link	c.196C>T	p.Arg66Cys	missense_variant	Exon 6 of 14	1	NM_001135022.2	ENSP00000387139.3		Q96FG2-1

Frequencies

GnomAD3 genomes

AF:

0.0620

AC:

9424

AN:

152116

Hom.:

559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0315

Gnomad ASJ

AF:

0.0259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00871

Gnomad FIN

AF:

0.0274

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0269

Gnomad OTH

AF:

0.0449

GnomAD3 exomes

AF:

0.0295

AC:

7390

AN:

250122

Hom.:

280

AF XY:

0.0258

AC XY:

3484

AN XY:

135138

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.0190

Gnomad ASJ exome

AF:

0.0250

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00617

Gnomad FIN exome

AF:

0.0313

Gnomad NFE exome

AF:

0.0245

Gnomad OTH exome

AF:

0.0295

GnomAD4 exome

AF:

0.0284

AC:

41170

AN:

1449106

Hom.:

981

Cov.:

AF XY:

0.0272

AC XY:

19609

AN XY:

721786

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.0212

Gnomad4 ASJ exome

AF:

0.0273

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00659

Gnomad4 FIN exome

AF:

0.0317

Gnomad4 NFE exome

AF:

0.0269

Gnomad4 OTH exome

AF:

0.0324

GnomAD4 genome

AF:

0.0620

AC:

9444

AN:

152234

Hom.:

563

Cov.:

AF XY:

0.0593

AC XY:

4411

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.0315

Gnomad4 ASJ

AF:

0.0259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00830

Gnomad4 FIN

AF:

0.0274

Gnomad4 NFE

AF:

0.0269

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0309

Hom.:

225

Bravo

AF:

0.0678

TwinsUK

AF:

0.0210

AC:

ALSPAC

AF:

0.0301

AC:

116

ESP6500AA

AF:

0.160

AC:

704

ESP6500EA

AF:

0.0263

AC:

226

ExAC

AF:

0.0320

AC:

3889

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0274

EpiControl

AF:

0.0274

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 24, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Aug 24, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.036

T;T;T;T;.;T;T;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.64

T;.;.;.;T;T;T;T

MetaRNN

Benign

0.0014

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

.;N;N;N;N;.;N;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.5

N;N;N;N;N;N;N;N

REVEL

Benign

0.041

Sift

Benign

0.049

D;T;T;T;D;T;T;T

Sift4G

Benign

0.069

T;T;T;T;T;T;T;T

Polyphen

0.52, 0.65

.;P;P;P;P;.;P;.

Vest4

0.19, 0.098

MPC

0.62

ClinPred

0.013

GERP RS

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.071

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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