11-107630714-G-A

Position:

• chr11-107630714-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018712.4(ELMOD1):​c.178G>A​(p.Asp60Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: ELMOD1 NM_018712.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05668339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELMOD1	NM_018712.4	c.178G>A	p.Asp60Asn	missense_variant	4/12	ENST00000265840.12	NP_061182.3
ELMOD1	NM_001308018.2	c.160G>A	p.Asp54Asn	missense_variant	5/13		NP_001294947.1
ELMOD1	NM_001130037.2	c.178G>A	p.Asp60Asn	missense_variant	4/11		NP_001123509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELMOD1	ENST00000265840.12	c.178G>A	p.Asp60Asn	missense_variant	4/12	1	NM_018712.4	ENSP00000265840.7
ELMOD1	ENST00000531234.5	c.160G>A	p.Asp54Asn	missense_variant	5/13	2		ENSP00000433232.1
ELMOD1	ENST00000443271.2	c.178G>A	p.Asp60Asn	missense_variant	4/11	2		ENSP00000412257.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 07, 2024

The c.178G>A (p.D60N) alteration is located in exon 4 (coding exon 3) of the ELMOD1 gene. This alteration results from a G to A substitution at nucleotide position 178, causing the aspartic acid (D) at amino acid position 60 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	0.071
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0031	T;T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	.;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.43	N;N;N
REVEL	Benign	0.036
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.33	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.14
MutPred		0.24		.;Loss of ubiquitination at K64 (P = 0.0283);Loss of ubiquitination at K64 (P = 0.0283);
MVP		0.043
MPC		0.092
ClinPred		0.40	T
GERP RS		4.7
Varity_R		0.064
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs754171634; hg19: chr11-107501440; COSMIC: COSV56191482;