11-107630714-G-C

Variant names:

• chr11-107630714-G-C
• rs754171634
• NM_018712.4:c.178G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018712.4(ELMOD1):​c.178G>C​(p.Asp60His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000622 in 1,606,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ELMOD1 NM_018712.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.89

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054381847).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMOD1	NM_018712.4	c.178G>C	p.Asp60His	missense_variant	Exon 4 of 12	ENST00000265840.12	NP_061182.3
ELMOD1	NM_001308018.2	c.160G>C	p.Asp54His	missense_variant	Exon 5 of 13		NP_001294947.1
ELMOD1	NM_001130037.2	c.178G>C	p.Asp60His	missense_variant	Exon 4 of 11		NP_001123509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELMOD1	ENST00000265840.12	c.178G>C	p.Asp60His	missense_variant	Exon 4 of 12	1	NM_018712.4	ENSP00000265840.7
ELMOD1	ENST00000531234.5	c.160G>C	p.Asp54His	missense_variant	Exon 5 of 13	2		ENSP00000433232.1
ELMOD1	ENST00000443271.2	c.178G>C	p.Asp60His	missense_variant	Exon 4 of 11	2		ENSP00000412257.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000619 AC: 9 AN: 1454556 Hom.: 0 Cov.: 31 AF XY: 0.00000830 AC XY: 6 AN XY: 722640

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000812

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152148 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74328

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000282 Hom.: 0

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.53
DEOGEN2	Benign	0.0041	T;T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.054	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.050	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.54	T;T;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.0010	.;B;.
Vest4		0.29
MutPred		0.25		.;Loss of ubiquitination at K62 (P = 0.0272);Loss of ubiquitination at K62 (P = 0.0272);
MVP		0.043
MPC		0.13
ClinPred		0.17	T
GERP RS		4.7
Varity_R		0.089
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs754171634; hg19: chr11-107501440;