11-107631667-G-C

Variant names:

• chr11-107631667-G-C
• rs915941934
• NM_018712.4:c.280G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018712.4(ELMOD1):​c.280G>C​(p.Val94Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000731 in 1,367,182 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. V94I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ELMOD1 NM_018712.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08978945).

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.280G>C	p.Val94Leu	missense	Exon 5 of 12	NP_061182.3
	ELMOD1	NM_001308018.2		c.262G>C	p.Val88Leu	missense	Exon 6 of 13	NP_001294947.1	E9PLM8
	ELMOD1	NM_001130037.2		c.280G>C	p.Val94Leu	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.280G>C	p.Val94Leu	missense	Exon 5 of 12	ENSP00000265840.7	Q8N336-1
	ELMOD1	ENST00000531234.5	TSL:2	c.262G>C	p.Val88Leu	missense	Exon 6 of 13	ENSP00000433232.1	E9PLM8
	ELMOD1	ENST00000443271.2	TSL:2	c.280G>C	p.Val94Leu	missense	Exon 5 of 11	ENSP00000412257.2	Q8N336-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.31e-7 AC: 1 AN: 1367182 Hom.: 0 Cov.: 25 AF XY: 0.00000148 AC XY: 1 AN XY: 676310

African (AFR) AF: 0.00 AC: 0 AN: 30700

American (AMR) AF: 0.00 AC: 0 AN: 34974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24894

East Asian (EAS) AF: 0.00 AC: 0 AN: 35598

South Asian (SAS) AF: 0.00 AC: 0 AN: 77386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 9.51e-7 AC: 1 AN: 1051676

Other (OTH) AF: 0.00 AC: 0 AN: 56868

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.6
DANN	Benign	0.75
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.82	L
PhyloP100		1.0
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.059
Sift	Benign	0.31	T
Sift4G	Benign	0.32	T
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.32		Gain of ubiquitination at K89 (P = 0.1128)
MVP		0.068
MPC		0.092
ClinPred		0.26	T
GERP RS		-2.1
Varity_R		0.052
gMVP		0.19
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs915941934; hg19: chr11-107502393;