Variant 11-107631610-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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. Variant has been reported in ClinVar 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

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/exons	MANE	Protein	UniProt
ELMOD1	NM_018712.4 linkuse as main transcript	c.223G>A	p.Asp75Asn	missense_variant	5/12	ENST00000265840.12	NP_061182.3	Q8N336-1
ELMOD1	NM_001308018.2 linkuse as main transcript	c.205G>A	p.Asp69Asn	missense_variant	6/13		NP_001294947.1	Q8N336E9PLM8B4DM88
ELMOD1	NM_001130037.2 linkuse as main transcript	c.223G>A	p.Asp75Asn	missense_variant	5/11		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.223G>A	p.Asp75Asn	missense_variant	5/12	1	NM_018712.4	ENSP00000265840.7	Q8N336-1
ELMOD1	ENST00000531234.5 linkuse as main transcript	c.205G>A	p.Asp69Asn	missense_variant	6/13	2		ENSP00000433232.1	E9PLM8
ELMOD1	ENST00000443271.2 linkuse as main transcript	c.223G>A	p.Asp75Asn	missense_variant	5/11	2		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

GnomAD4 exome

AF:

0.00000991

AC:

AN:

1413196

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

698396

show subpopulations

Gnomad4 AFR exome

AF:

0.0000312

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:

0.0000120

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151916

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

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

Nov 21, 2022

The c.223G>A (p.D75N) alteration is located in exon 5 (coding exon 4) of the ELMOD1 gene. This alteration results from a G to A substitution at nucleotide position 223, causing the aspartic acid (D) at amino acid position 75 to be replaced by an asparagine (N). 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

Benign

0.15

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

T;T;.

Eigen

Benign

0.044

Eigen_PC

Benign

0.22

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.0091

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

.;L;L

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.50

N;N;N

REVEL

Benign

0.070

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.055

.;B;.

Vest4

0.74

MutPred

0.28

.;Loss of catalytic residue at D75 (P = 0.0974);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

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

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