11-107655982-C-A

Position:

• chr11-107655982-C-A

Variant summary

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

The NM_018712.4(ELMOD1):​c.748C>A​(p.Leu250Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ELMOD1 NM_018712.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72

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.748C>A	p.Leu250Ile	missense_variant	11/12	ENST00000265840.12	NP_061182.3
ELMOD1	NM_001308018.2	c.730C>A	p.Leu244Ile	missense_variant	12/13		NP_001294947.1
ELMOD1	NM_001130037.2	c.724C>A	p.Leu242Ile	missense_variant	10/11		NP_001123509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELMOD1	ENST00000265840.12	c.748C>A	p.Leu250Ile	missense_variant	11/12	1	NM_018712.4	ENSP00000265840.7
ELMOD1	ENST00000531234.5	c.730C>A	p.Leu244Ile	missense_variant	12/13	2		ENSP00000433232.1
ELMOD1	ENST00000443271.2	c.724C>A	p.Leu242Ile	missense_variant	10/11	2		ENSP00000412257.2
ELMOD1	ENST00000534236.1	n.837C>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1445364 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 717138

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

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

Oct 26, 2022

The c.748C>A (p.L250I) alteration is located in exon 11 (coding exon 10) of the ELMOD1 gene. This alteration results from a C to A substitution at nucleotide position 748, causing the leucine (L) at amino acid position 250 to be replaced by an isoleucine (I). 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	Uncertain	0.46
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T;T;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.3	.;M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.96	.;D;.
Vest4		0.67
MutPred		0.78		.;Gain of glycosylation at S253 (P = 0.1657);.;
MVP		0.23
MPC		0.51
ClinPred		0.91	D
GERP RS		6.0
Varity_R		0.40
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr11-107526708;