rs144700377

Variant names:

• chr7-37211429-C-A
• rs144700377
• NM_014800.11:c.1043G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-37211429-C-A
• chr7-37211429-C-T

Variant summary

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

The NM_014800.11(ELMO1):​c.1043G>T​(p.Arg348Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,754 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. R348H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ELMO1 NM_014800.11 missense
• Clinical Significance: Not reported in ClinVar
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.802

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMO1	NM_014800.11	c.1043G>T	p.Arg348Leu	missense_variant	Exon 13 of 22	ENST00000310758.9	NP_055615.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELMO1	ENST00000310758.9	c.1043G>T	p.Arg348Leu	missense_variant	Exon 13 of 22	1	NM_014800.11	ENSP00000312185.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461754 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727168

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111948

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T;T;T;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	.;.;D;D
M_CAP	Benign	0.036	D
MetaRNN	Pathogenic	0.80	D;D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M;M;M;.
PhyloP100		7.9
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.026	D;D;D;D
Sift4G	Benign	0.13	T;T;T;D
Polyphen		0.99	D;D;D;.
Vest4		0.76
MutPred		0.72		Gain of ubiquitination at K347 (P = 0.0315);Gain of ubiquitination at K347 (P = 0.0315);Gain of ubiquitination at K347 (P = 0.0315);.;
MVP		0.67
MPC		2.1
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.57
gMVP		0.60
Mutation Taster		=30/70	disease causing

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: rs144700377; hg19: chr7-37251034;