Genetic Variant ELMOD1:p.Arg34Ser (chr11-107630501-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018712.4(ELMOD1):c.102A>T(p.Arg34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,457,806 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ELMOD1
NM_018712.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.676

Variant links:

Genes affected

ELMOD1 (HGNC:25334): (ELMO domain containing 1) Enables GTPase activator activity. Predicted to be involved in positive regulation of GTPase activity. [provided by Alliance of Genome Resources, Apr 2022]

ELMOD1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMOD1	NM_018712.4 link	c.102A>T	p.Arg34Ser	missense_variant	Exon 3 of 12	ENST00000265840.12	NP_061182.3	Q8N336-1
ELMOD1	NM_001308018.2 link	c.84A>T	p.Arg28Ser	missense_variant	Exon 4 of 13		NP_001294947.1	Q8N336E9PLM8B4DM88
ELMOD1	NM_001130037.2 link	c.102A>T	p.Arg34Ser	missense_variant	Exon 3 of 11		NP_001123509.1	Q8N336-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ELMOD1	ENST00000265840.12 link	c.102A>T	p.Arg34Ser	missense_variant	Exon 3 of 12	1	NM_018712.4	ENSP00000265840.7	Q8N336-1
ELMOD1	ENST00000531234.5 link	c.84A>T	p.Arg28Ser	missense_variant	Exon 4 of 13	2		ENSP00000433232.1	E9PLM8
ELMOD1	ENST00000443271.2 link	c.102A>T	p.Arg34Ser	missense_variant	Exon 3 of 11	2		ENSP00000412257.2	Q8N336-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000413

AC:

AN:

242154

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130938

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000570

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1457806

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724574

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000996

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.102A>T (p.R34S) alteration is located in exon 3 (coding exon 2) of the ELMOD1 gene. This alteration results from a A to T substitution at nucleotide position 102, causing the arginine (R) at amino acid position 34 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

T;T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.85

D;T;D

M_CAP

Benign

0.0079

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.15

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.015

.;B;.

Vest4

0.76

MutPred

0.45

.;Loss of MoRF binding (P = 0.0357);Loss of MoRF binding (P = 0.0357);

MVP

0.53

MPC

0.20

ClinPred

0.094

GERP RS

0.24

Varity_R

0.22

gMVP

0.71

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

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