7-37216661-C-T

Variant names:

• chr7-37216661-C-T
• rs1448608892
• NM_014800.11:c.815G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014800.11(ELMO1):​c.815G>A​(p.Arg272His) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,836 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. R272L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ELMO1 NM_014800.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.87
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.759

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.815G>A	p.Arg272His	missense	Exon 11 of 22	NP_055615.8
	ELMO1	NM_001206480.2		c.815G>A	p.Arg272His	missense	Exon 11 of 22	NP_001193409.1	A4D1X5
	ELMO1	NM_001206482.2		c.815G>A	p.Arg272His	missense	Exon 11 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.815G>A	p.Arg272His	missense	Exon 11 of 22	ENSP00000312185.4	Q92556-1
	ELMO1	ENST00000448602.5	TSL:1	c.815G>A	p.Arg272His	missense	Exon 11 of 22	ENSP00000394458.1	Q92556-1
	ELMO1	ENST00000442504.5	TSL:2	c.815G>A	p.Arg272His	missense	Exon 11 of 22	ENSP00000406952.1	Q92556-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461836 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727220

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111968

Other (OTH) AF: 0.00 AC: 0 AN: 60394

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	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		6.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.55		Loss of MoRF binding (P = 0.0116)
MVP		0.66
MPC		2.0
ClinPred		1.0	D
GERP RS		4.6
PromoterAI		0.051	Neutral
Varity_R		0.60
gMVP		0.71
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs1448608892; hg19: chr7-37256266; COSMIC: COSV60308604;