chr11-107635683-G-C

Variant names:

• chr11-107635683-G-C
• rs750774743
• NM_018712.4:c.338G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018712.4(ELMOD1):​c.338G>C​(p.Arg113Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,612 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ELMOD1 NM_018712.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.09
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018712.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMOD1	NM_018712.4	MANE Select	c.338G>C	p.Arg113Thr	missense	Exon 6 of 12	NP_061182.3
	ELMOD1	NM_001308018.2		c.320G>C	p.Arg107Thr	missense	Exon 7 of 13	NP_001294947.1	E9PLM8
	ELMOD1	NM_001130037.2		c.338G>C	p.Arg113Thr	missense	Exon 6 of 11	NP_001123509.1	Q8N336-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELMOD1	ENST00000265840.12	TSL:1 MANE Select	c.338G>C	p.Arg113Thr	missense	Exon 6 of 12	ENSP00000265840.7	Q8N336-1
	ELMOD1	ENST00000531234.5	TSL:2	c.320G>C	p.Arg107Thr	missense	Exon 7 of 13	ENSP00000433232.1	E9PLM8
	ELMOD1	ENST00000443271.2	TSL:2	c.338G>C	p.Arg113Thr	missense	Exon 6 of 11	ENSP00000412257.2	Q8N336-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000803 AC: 2 AN: 249080 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461612 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727090

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111808

Other (OTH) AF: 0.0000497 AC: 3 AN: 60368

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.33
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.065	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		9.1
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.27
Sift	Benign	0.070	T
Sift4G	Benign	0.11	T
Polyphen		0.23	B
Vest4		0.94
MutPred		0.51		Loss of helix (P = 0.1299)
MVP		0.18
MPC		0.59
ClinPred		0.80	D
GERP RS		5.6
Varity_R		0.41
gMVP		0.69
Mutation Taster		=12/88	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs750774743; hg19: chr11-107506409;