Genetic Variant NM_153702.4:c.116T>C (chr4-140525544-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153702.4(ELMOD2):c.116T>C(p.Val39Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V39G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ELMOD2
NM_153702.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.685

Publications

0 publications found

Variant links:

Genes affected

ELMOD2 (HGNC:28111): (ELMO domain containing 2) This gene encodes one of six engulfment and motility (ELMO) domain-containing proteins. This gene is thought to play a role in antiviral responses. Mutations in this gene may be involved in the cause of familial idiopathic pulmonary fibrosis. [provided by RefSeq, Sep 2010]

ELMOD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031616837).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMOD2	NM_153702.4 link	c.116T>C	p.Val39Ala	missense_variant	Exon 2 of 9	ENST00000323570.8	NP_714913.1	Q8IZ81

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELMOD2	ENST00000323570.8 link	c.116T>C	p.Val39Ala	missense_variant	Exon 2 of 9	1	NM_153702.4	ENSP00000326342.3		Q8IZ81

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461038

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726776

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33410

American (AMR)

AF:

0.00

AC:

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39614

South Asian (SAS)

AF:

0.00

AC:

AN:

86056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111744

Other (OTH)

AF:

0.00

AC:

AN:

60362

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.0084

T;T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.18

T;T;T

M_CAP

Benign

0.00099

MetaRNN

Benign

0.032

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;.

PhyloP100

0.69

PrimateAI

Benign

0.39

PROVEAN

Benign

0.98

N;.;N

REVEL

Benign

0.018

Sift

Benign

0.64

T;.;T

Sift4G

Benign

0.88

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.22

MutPred

0.28

Gain of catalytic residue at V39 (P = 0.052);Gain of catalytic residue at V39 (P = 0.052);Gain of catalytic residue at V39 (P = 0.052);

MVP

0.082

MPC

0.047

ClinPred

0.055

GERP RS

2.4

Varity_R

0.017

gMVP

0.36

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over