Genetic Variant NM_018712.4:c.223G>A (chr11-107631610-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018712.4(ELMOD1):c.223G>A(p.Asp75Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000115 in 1,565,112 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D75E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000099 ( 0 hom. )

Consequence

ELMOD1
NM_018712.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.01

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.223G>A	p.Asp75Asn	missense	Exon 5 of 12	NP_061182.3
ELMOD1	NM_001308018.2		c.205G>A	p.Asp69Asn	missense	Exon 6 of 13	NP_001294947.1	E9PLM8
ELMOD1	NM_001130037.2		c.223G>A	p.Asp75Asn	missense	Exon 5 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.223G>A	p.Asp75Asn	missense	Exon 5 of 12	ENSP00000265840.7	Q8N336-1
ELMOD1	ENST00000531234.5	TSL:2	c.205G>A	p.Asp69Asn	missense	Exon 6 of 13	ENSP00000433232.1	E9PLM8
ELMOD1	ENST00000443271.2	TSL:2	c.223G>A	p.Asp75Asn	missense	Exon 5 of 11	ENSP00000412257.2	Q8N336-3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

180004

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000991

AC:

AN:

1413196

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

698396

show subpopulations

African (AFR)

AF:

0.0000312

AC:

AN:

32096

American (AMR)

AF:

0.00

AC:

AN:

37818

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25338

East Asian (EAS)

AF:

0.00

AC:

AN:

37406

South Asian (SAS)

AF:

0.00

AC:

AN:

79456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.0000120

AC:

AN:

1086368

Other (OTH)

AF:

0.00

AC:

AN:

58582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

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

AF:

0.0000263

AC:

AN:

151916

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41358

American (AMR)

AF:

0.0000656

AC:

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67962

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

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

Benign

0.15

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Benign

0.044

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.0091

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

PhyloP100

9.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.50

REVEL

Benign

0.070

Sift

Benign

0.21

Sift4G

Benign

0.26

Polyphen

0.055

Vest4

0.74

MutPred

0.28

Loss of catalytic residue at D75 (P = 0.0974)

MVP

0.19

MPC

0.48

ClinPred

0.96

GERP RS

5.7

Varity_R

0.091

gMVP

0.52

Mutation Taster

=24/76

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over