11-107635694-G-A

Position:

• chr11-107635694-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018712.4(ELMOD1):​c.349G>A​(p.Ala117Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ELMOD1 NM_018712.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.28

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 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=0.2523921).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELMOD1	NM_018712.4	c.349G>A	p.Ala117Thr	missense_variant	6/12	ENST00000265840.12	NP_061182.3
ELMOD1	NM_001308018.2	c.331G>A	p.Ala111Thr	missense_variant	7/13		NP_001294947.1
ELMOD1	NM_001130037.2	c.349G>A	p.Ala117Thr	missense_variant	6/11		NP_001123509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELMOD1	ENST00000265840.12	c.349G>A	p.Ala117Thr	missense_variant	6/12	1	NM_018712.4	ENSP00000265840.7
ELMOD1	ENST00000531234.5	c.331G>A	p.Ala111Thr	missense_variant	7/13	2		ENSP00000433232.1
ELMOD1	ENST00000443271.2	c.349G>A	p.Ala117Thr	missense_variant	6/11	2		ENSP00000412257.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461652 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727118

Gnomad4 AFR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Nov 26, 2024

The c.349G>A (p.A117T) alteration is located in exon 6 (coding exon 5) of the ELMOD1 gene. This alteration results from a G to A substitution at nucleotide position 349, causing the alanine (A) at amino acid position 117 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	0.076
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T;T;.
Eigen	Benign	-0.0066
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D;D;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.86	N;N;N
REVEL	Benign	0.091
Sift	Benign	0.39	T;T;T
Sift4G	Benign	0.39	T;T;T
Polyphen		0.019	.;B;.
Vest4		0.48
MutPred		0.32		.;Loss of stability (P = 0.0457);Loss of stability (P = 0.0457);
MVP		0.093
MPC		0.21
ClinPred		0.71	D
GERP RS		5.6
Varity_R		0.14
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1866217384; hg19: chr11-107506420;