11-107650343-C-A

Variant names:

• chr11-107650343-C-A
• rs763943002
• NM_018712.4:c.563C>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_018712.4(ELMOD1):​c.563C>A​(p.Ala188Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,432,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A188V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ELMOD1 NM_018712.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.06
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.973

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018712.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMOD1	NM_018712.4	MANE Select	c.563C>A	p.Ala188Glu	missense	Exon 8 of 12	NP_061182.3
	ELMOD1	NM_001308018.2		c.545C>A	p.Ala182Glu	missense	Exon 9 of 13	NP_001294947.1	E9PLM8
	ELMOD1	NM_001130037.2		c.563C>A	p.Ala188Glu	missense	Exon 8 of 11	NP_001123509.1	Q8N336-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMOD1	ENST00000265840.12	TSL:1 MANE Select	c.563C>A	p.Ala188Glu	missense	Exon 8 of 12	ENSP00000265840.7	Q8N336-1
	ELMOD1	ENST00000531234.5	TSL:2	c.545C>A	p.Ala182Glu	missense	Exon 9 of 13	ENSP00000433232.1	E9PLM8
	ELMOD1	ENST00000443271.2	TSL:2	c.563C>A	p.Ala188Glu	missense	Exon 8 of 11	ENSP00000412257.2	Q8N336-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432166 Hom.: 0 Cov.: 29 AF XY: 0.00000141 AC XY: 1 AN XY: 708892

African (AFR) AF: 0.00 AC: 0 AN: 32946

American (AMR) AF: 0.00 AC: 0 AN: 40962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25518

East Asian (EAS) AF: 0.00 AC: 0 AN: 38738

South Asian (SAS) AF: 0.00 AC: 0 AN: 81340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095640

Other (OTH) AF: 0.00 AC: 0 AN: 59422

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		5.1
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.87	P
Vest4		0.92
MutPred		0.89		Gain of relative solvent accessibility (P = 0.09)
MVP		0.45
MPC		0.44
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.76
gMVP		0.90
Mutation Taster		=24/76	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs763943002; hg19: chr11-107521069;