chr11-107650343-C-A

Variant names:

• chr11-107650343-C-A
• NM_018712.4:c.563C>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_018712.4(ELMOD1):​c.563C>A​(p.Ala188Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,432,166 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ELMOD1 NM_018712.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.06

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.973

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMOD1	NM_018712.4	c.563C>A	p.Ala188Glu	missense_variant	Exon 8 of 12	ENST00000265840.12	NP_061182.3
ELMOD1	NM_001308018.2	c.545C>A	p.Ala182Glu	missense_variant	Exon 9 of 13		NP_001294947.1
ELMOD1	NM_001130037.2	c.563C>A	p.Ala188Glu	missense_variant	Exon 8 of 11		NP_001123509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELMOD1	ENST00000265840.12	c.563C>A	p.Ala188Glu	missense_variant	Exon 8 of 12	1	NM_018712.4	ENSP00000265840.7
ELMOD1	ENST00000531234.5	c.545C>A	p.Ala182Glu	missense_variant	Exon 9 of 13	2		ENSP00000433232.1
ELMOD1	ENST00000443271.2	c.563C>A	p.Ala188Glu	missense_variant	Exon 8 of 11	2		ENSP00000412257.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432166 Hom.: 0 Cov.: 29 AF XY: 0.00000141 AC XY: 1 AN XY: 708892

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: 9.13e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T;T;.
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Pathogenic	3.4	.;M;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		0.87	.;P;.
Vest4		0.92
MutPred		0.89		.;Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP		0.45
MPC		0.44
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.76
gMVP		0.90

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-107521069;