NM_018712.4:c.223G>C

Variant names:

• chr11-107631610-G-C
• rs940135118
• NM_018712.4:c.223G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018712.4(ELMOD1):​c.223G>C​(p.Asp75His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. D75E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELMOD1 NM_018712.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.01
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.223G>C	p.Asp75His	missense	Exon 5 of 12	NP_061182.3
	ELMOD1	NM_001308018.2		c.205G>C	p.Asp69His	missense	Exon 6 of 13	NP_001294947.1	E9PLM8
	ELMOD1	NM_001130037.2		c.223G>C	p.Asp75His	missense	Exon 5 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.223G>C	p.Asp75His	missense	Exon 5 of 12	ENSP00000265840.7	Q8N336-1
	ELMOD1	ENST00000531234.5	TSL:2	c.205G>C	p.Asp69His	missense	Exon 6 of 13	ENSP00000433232.1	E9PLM8
	ELMOD1	ENST00000443271.2	TSL:2	c.223G>C	p.Asp75His	missense	Exon 5 of 11	ENSP00000412257.2	Q8N336-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		9.0
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.20
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.032	D
Polyphen		0.93	P
Vest4		0.82
MutPred		0.29		Loss of helix (P = 0.1299)
MVP		0.25
MPC		0.53
ClinPred		0.93	D
GERP RS		5.7
Varity_R		0.17
gMVP		0.65
Mutation Taster		=33/67	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.23		Position offset: -30

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

Other links and lift over

dbSNP: rs940135118; hg19: chr11-107502336;