rs5030739

Variant names:

• chr17-12996585-C-A
• rs5030739
• NM_018127.7:c.1621G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-12996585-C-A
• chr17-12996585-C-G
• chr17-12996585-C-T

Variant summary

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

The NM_018127.7(ELAC2):​c.1621G>T​(p.Ala541Ser) variant causes a missense change. 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. A541T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ELAC2 NM_018127.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• Publications: 0 publications found

Genes affected

ELAC2 (HGNC:14198): (elaC ribonuclease Z 2) The protein encoded by this gene has a C-terminal domain with tRNA 3′ processing endoribonuclease activity, which catalyzes the removal of the 3' trailer from precursor tRNAs. The protein also interacts with activated Smad family member 2 (Smad2) and its nuclear partner forkhead box H1 (also known as FAST-1), and reduced expression can suppress transforming growth factor-beta induced growth arrest. Mutations in this gene result in an increased risk of prostate cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ELAC2 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation defect type 17

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

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_018127.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC2	NM_018127.7	MANE Select	c.1621G>T	p.Ala541Ser	missense	Exon 17 of 24	NP_060597.4
	ELAC2	NM_173717.2		c.1618G>T	p.Ala540Ser	missense	Exon 17 of 24	NP_776065.1
	ELAC2	NM_001165962.2		c.1501G>T	p.Ala501Ser	missense	Exon 16 of 23	NP_001159434.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC2	ENST00000338034.9	TSL:1 MANE Select	c.1621G>T	p.Ala541Ser	missense	Exon 17 of 24	ENSP00000337445.4
	ELAC2	ENST00000395962.6	TSL:2	c.1564G>T	p.Ala522Ser	missense	Exon 17 of 24	ENSP00000379291.1
	ELAC2	ENST00000426905.7	TSL:2	c.1501G>T	p.Ala501Ser	missense	Exon 16 of 23	ENSP00000405223.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Benign	0.87
DEOGEN2	Benign	0.055	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.29
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.042	D
Polyphen		0.78	P
Vest4		0.50
MutPred		0.43		Loss of stability (P = 0.1517)
MVP		0.82
MPC		0.28
ClinPred		0.63	D
GERP RS		5.6
Varity_R		0.33
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5030739; hg19: chr17-12899902;