7-37211489-C-A

Variant names:

• chr7-37211489-C-A
• rs1174488092
• NM_014800.11:c.983G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014800.11(ELMO1):​c.983G>T​(p.Arg328Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELMO1 NM_014800.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

Genes affected

ELMO1 (HGNC:16286): (engulfment and cell motility 1) This gene encodes a member of the engulfment and cell motility protein family. These proteins interact with dedicator of cytokinesis proteins to promote phagocytosis and cell migration. Increased expression of this gene and dedicator of cytokinesis 1 may promote glioma cell invasion, and single nucleotide polymorphisms in this gene may be associated with diabetic nephropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ELMO1 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014800.11. 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
	ELMO1	NM_014800.11	MANE Select	c.983G>T	p.Arg328Leu	missense	Exon 13 of 22	NP_055615.8
	ELMO1	NM_001206480.2		c.983G>T	p.Arg328Leu	missense	Exon 13 of 22	NP_001193409.1	A4D1X5
	ELMO1	NM_001206482.2		c.983G>T	p.Arg328Leu	missense	Exon 13 of 22	NP_001193411.1	Q92556-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMO1	ENST00000310758.9	TSL:1 MANE Select	c.983G>T	p.Arg328Leu	missense	Exon 13 of 22	ENSP00000312185.4	Q92556-1
	ELMO1	ENST00000448602.5	TSL:1	c.983G>T	p.Arg328Leu	missense	Exon 13 of 22	ENSP00000394458.1	Q92556-1
	ELMO1	ENST00000442504.5	TSL:2	c.983G>T	p.Arg328Leu	missense	Exon 13 of 22	ENSP00000406952.1	Q92556-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.67		Gain of catalytic residue at R328 (P = 0.0297)
MVP		0.53
MPC		2.0
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.80
gMVP		0.80
Mutation Taster		=36/64	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: rs1174488092; hg19: chr7-37251094;