Variant 11-107665046-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018712.4(ELMOD1):c.854A>G(p.His285Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,194 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ELMOD1
NM_018712.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.66

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.86

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELMOD1	NM_018712.4 linkuse as main transcript	c.854A>G	p.His285Arg	missense_variant	12/12	ENST00000265840.12	NP_061182.3	Q8N336-1
ELMOD1	NM_001308018.2 linkuse as main transcript	c.836A>G	p.His279Arg	missense_variant	13/13		NP_001294947.1	Q8N336E9PLM8B4DM88
ELMOD1	NM_001130037.2 linkuse as main transcript	c.830A>G	p.His277Arg	missense_variant	11/11		NP_001123509.1	Q8N336-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ELMOD1	ENST00000265840.12 linkuse as main transcript	c.854A>G	p.His285Arg	missense_variant	12/12	1	NM_018712.4	ENSP00000265840.7	Q8N336-1
ELMOD1	ENST00000531234.5 linkuse as main transcript	c.836A>G	p.His279Arg	missense_variant	13/13	2		ENSP00000433232.1	E9PLM8
ELMOD1	ENST00000443271.2 linkuse as main transcript	c.830A>G	p.His277Arg	missense_variant	11/11	2		ENSP00000412257.2	Q8N336-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000241

AC:

AN:

248634

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461194

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726842

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.854A>G (p.H285R) alteration is located in exon 12 (coding exon 11) of the ELMOD1 gene. This alteration results from a A to G substitution at nucleotide position 854, causing the histidine (H) at amino acid position 285 to be replaced by an arginine (R). 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

0.86

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.010

MetaRNN

Pathogenic

0.86

D;D;D

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.5

.;M;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.4

N;N;N

REVEL

Uncertain

0.30

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

0.95

.;P;.

Vest4

0.75

MutPred

0.81

.;Gain of helix (P = 0.0696);.;

MVP

0.24

MPC

0.37

ClinPred

0.45

GERP RS

6.0

Varity_R

0.35

gMVP

0.85

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