18-50984473-C-G

Variant names:

• chr18-50984473-C-G
• rs139447573
• NM_018696.3:c.535C>G

Variant summary

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

The NM_018696.3(ELAC1):​c.535C>G​(p.Arg179Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R179L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELAC1 NM_018696.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.84
• Publications: 0 publications found

Genes affected

ELAC1 (HGNC:14197): (elaC ribonuclease Z 1) Predicted to enable 3'-tRNA processing endoribonuclease activity. Predicted to be involved in tRNA 3'-trailer cleavage, endonucleolytic. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267699 (HGNC:):

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_018696.3. 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
	ELAC1	NM_018696.3	MANE Select	c.535C>G	p.Arg179Gly	missense	Exon 3 of 4	NP_061166.1	Q9H777

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC1	ENST00000269466.8	TSL:1 MANE Select	c.535C>G	p.Arg179Gly	missense	Exon 3 of 4	ENSP00000269466.3	Q9H777
	ELAC1	ENST00000591429.1	TSL:1	c.535C>G	p.Arg179Gly	missense	Exon 3 of 3	ENSP00000464770.1	K7EIJ1
	ENSG00000267699	ENST00000590722.2	TSL:2	n.157+9912C>G		intron	N/A	ENSP00000465737.1	E7EUB6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	0.050
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.42
Sift	Benign	0.44	T
Sift4G	Benign	0.41	T
Polyphen		0.0010	B
Vest4		0.91
MutPred		0.58		Loss of MoRF binding (P = 0.0123)
MVP		0.54
MPC		0.11
ClinPred		0.87	D
GERP RS		6.0
Varity_R		0.83
gMVP		0.81
Mutation Taster		=38/62	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: rs139447573; hg19: chr18-48510843;