Variant 11-107631613-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018712.4(ELMOD1):c.226G>A(p.Ala76Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000287 in 1,565,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

ELMOD1
NM_018712.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.193456).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELMOD1	NM_018712.4 linkuse as main transcript	c.226G>A	p.Ala76Thr	missense_variant	5/12	ENST00000265840.12	NP_061182.3	Q8N336-1
ELMOD1	NM_001308018.2 linkuse as main transcript	c.208G>A	p.Ala70Thr	missense_variant	6/13		NP_001294947.1	Q8N336E9PLM8B4DM88
ELMOD1	NM_001130037.2 linkuse as main transcript	c.226G>A	p.Ala76Thr	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.226G>A	p.Ala76Thr	missense_variant	5/12	1	NM_018712.4	ENSP00000265840.7	Q8N336-1
ELMOD1	ENST00000531234.5 linkuse as main transcript	c.208G>A	p.Ala70Thr	missense_variant	6/13	2		ENSP00000433232.1	E9PLM8
ELMOD1	ENST00000443271.2 linkuse as main transcript	c.226G>A	p.Ala76Thr	missense_variant	5/11	2		ENSP00000412257.2	Q8N336-3

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151936

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000297

AC:

AN:

1413554

Hom.:

Cov.:

AF XY:

0.0000243

AC XY:

AN XY:

698612

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

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:

0.0000377

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151936

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000151

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000272

AC:

ESP6500EA

AF:

0.00

AC:

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

Dec 03, 2021

The c.226G>A (p.A76T) 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 226, causing the alanine (A) at amino acid position 76 to be replaced by a threonine (T). 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

0.082

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.010

T;T;.

Eigen

Benign

0.044

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.0057

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

.;L;L

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.68

N;N;N

REVEL

Benign

0.081

Sift

Benign

0.49

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.47

.;P;.

Vest4

0.33

MVP

0.13

MPC

0.16

ClinPred

0.24

GERP RS

5.7

Varity_R

0.063

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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