11-107656019-A-T

Variant names:

• chr11-107656019-A-T
• rs766481819
• NM_018712.4:c.785A>T

Variant summary

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

The NM_018712.4(ELMOD1):​c.785A>T​(p.Asn262Ile) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ELMOD1 NM_018712.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.95

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, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELMOD1	NM_018712.4	c.785A>T	p.Asn262Ile	missense_variant	Exon 11 of 12	ENST00000265840.12	NP_061182.3
ELMOD1	NM_001308018.2	c.767A>T	p.Asn256Ile	missense_variant	Exon 12 of 13		NP_001294947.1
ELMOD1	NM_001130037.2	c.761A>T	p.Asn254Ile	missense_variant	Exon 10 of 11		NP_001123509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELMOD1	ENST00000265840.12	c.785A>T	p.Asn262Ile	missense_variant	Exon 11 of 12	1	NM_018712.4	ENSP00000265840.7
ELMOD1	ENST00000531234.5	c.767A>T	p.Asn256Ile	missense_variant	Exon 12 of 13	2		ENSP00000433232.1
ELMOD1	ENST00000443271.2	c.761A>T	p.Asn254Ile	missense_variant	Exon 10 of 11	2		ENSP00000412257.2
ELMOD1	ENST00000534236.1	n.*26A>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;T;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Pathogenic	0.94	D;D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.6	.;M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-7.1	D;D;D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.96
MutPred		0.78		.;Loss of disorder (P = 0.0722);.;
MVP		0.28
MPC		0.44
ClinPred		1.0	D
GERP RS		6.2
Varity_R		0.93
gMVP		0.71

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

LitVar

Other links and lift over

dbSNP: rs766481819; hg19: chr11-107526745;