Genetic Variant ELMOD1:p.His285Arg (chr11-107665046-A-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.86

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018712.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELMOD1	NM_018712.4	MANE Select	c.854A>G	p.His285Arg	missense	Exon 12 of 12	NP_061182.3
ELMOD1	NM_001308018.2		c.836A>G	p.His279Arg	missense	Exon 13 of 13	NP_001294947.1	E9PLM8
ELMOD1	NM_001130037.2		c.830A>G	p.His277Arg	missense	Exon 11 of 11	NP_001123509.1	Q8N336-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELMOD1	ENST00000265840.12	TSL:1 MANE Select	c.854A>G	p.His285Arg	missense	Exon 12 of 12	ENSP00000265840.7	Q8N336-1
ELMOD1	ENST00000531234.5	TSL:2	c.836A>G	p.His279Arg	missense	Exon 13 of 13	ENSP00000433232.1	E9PLM8
ELMOD1	ENST00000443271.2	TSL:2	c.830A>G	p.His277Arg	missense	Exon 11 of 11	ENSP00000412257.2	Q8N336-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000241

AC:

AN:

248634

AF XY:

0.0000297

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 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

African (AFR)

AF:

0.00

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86152

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000990

AC:

AN:

1111596

Other (OTH)

AF:

0.00

AC:

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.010

MetaRNN

Pathogenic

0.86

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.5

PhyloP100

8.7

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.30

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.017

Polyphen

0.95

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

Mutation Taster

=35/65

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over