11-107654186-C-T

Position:

• chr11-107654186-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018712.4(ELMOD1):​c.662C>T​(p.Ala221Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELMOD1 NM_018712.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87

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]

ELMOD1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELMOD1	NM_018712.4	c.662C>T	p.Ala221Val	missense_variant	10/12	ENST00000265840.12	NP_061182.3
ELMOD1	NM_001308018.2	c.644C>T	p.Ala215Val	missense_variant	11/13		NP_001294947.1
ELMOD1	NM_001130037.2	c.638C>T	p.Ala213Val	missense_variant	9/11		NP_001123509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELMOD1	ENST00000265840.12	c.662C>T	p.Ala221Val	missense_variant	10/12	1	NM_018712.4	ENSP00000265840.7
ELMOD1	ENST00000531234.5	c.644C>T	p.Ala215Val	missense_variant	11/13	2		ENSP00000433232.1
ELMOD1	ENST00000443271.2	c.638C>T	p.Ala213Val	missense_variant	9/11	2		ENSP00000412257.2
ELMOD1	ENST00000534236.1	n.751C>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.662C>T (p.A221V) alteration is located in exon 10 (coding exon 9) of the ELMOD1 gene. This alteration results from a C to T substitution at nucleotide position 662, causing the alanine (A) at amino acid position 221 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	0.038
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.073	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	.;M;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.070	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.49	T;T;T
Sift4G	Benign	0.51	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.11
MutPred		0.36		.;Loss of helix (P = 0.0138);.;
MVP		0.082
MPC		0.092
ClinPred		0.69	D
GERP RS		4.4
Varity_R		0.028
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.38		Position offset: -14

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: chr11-107524912;