11-107630448-T-C

Variant names:

• chr11-107630448-T-C
• rs547709819
• NM_018712.4:c.49T>C

Variant summary

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

The NM_018712.4(ELMOD1):​c.49T>C​(p.Cys17Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,844 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C17G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ELMOD1 NM_018712.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.49
• 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.49T>C	p.Cys17Arg	missense	Exon 3 of 12	NP_061182.3
	ELMOD1	NM_001308018.2		c.31T>C	p.Cys11Arg	missense	Exon 4 of 13	NP_001294947.1	E9PLM8
	ELMOD1	NM_001130037.2		c.49T>C	p.Cys17Arg	missense	Exon 3 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.49T>C	p.Cys17Arg	missense	Exon 3 of 12	ENSP00000265840.7	Q8N336-1
	ELMOD1	ENST00000531234.5	TSL:2	c.31T>C	p.Cys11Arg	missense	Exon 4 of 13	ENSP00000433232.1	E9PLM8
	ELMOD1	ENST00000443271.2	TSL:2	c.49T>C	p.Cys17Arg	missense	Exon 3 of 11	ENSP00000412257.2	Q8N336-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1450844 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 720290

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 43022

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25876

East Asian (EAS) AF: 0.00 AC: 0 AN: 39478

South Asian (SAS) AF: 0.00 AC: 0 AN: 84090

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106316

Other (OTH) AF: 0.00 AC: 0 AN: 60026

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Benign	22
DANN	Uncertain	0.97
DEOGEN2	Benign	0.035	T
Eigen	Benign	0.031
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0055	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.5
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.31
Sift	Benign	0.38	T
Sift4G	Benign	0.40	T
Polyphen		0.012	B
Vest4		0.93
MutPred		0.58		Gain of MoRF binding (P = 0.0394)
MVP		0.15
MPC		0.65
ClinPred		0.91	D
GERP RS		5.5
Varity_R		0.60
gMVP		0.77
Mutation Taster		=2/98	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: rs547709819; hg19: chr11-107501174;