17-12996646-T-C

Variant names:

• chr17-12996646-T-C
• rs11545302
• NM_018127.7:c.1560A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_018127.7(ELAC2):​c.1560A>G​(p.Thr520Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,613,436 control chromosomes in the GnomAD database, including 69,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T520T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.27 (5692 hom., cov: 32)
  • Exomes 𝑓: 0.29 (63634 hom.)
• Consequence: ELAC2 NM_018127.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.71
• Publications: 21 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 17-12996646-T-C is Benign according to our data. Variant chr17-12996646-T-C is described in ClinVar as Benign. ClinVar VariationId is 379971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC2	NM_018127.7	MANE Select	c.1560A>G	p.Thr520Thr	synonymous	Exon 17 of 24	NP_060597.4
	ELAC2	NM_173717.2		c.1557A>G	p.Thr519Thr	synonymous	Exon 17 of 24	NP_776065.1
	ELAC2	NM_001165962.2		c.1440A>G	p.Thr480Thr	synonymous	Exon 16 of 23	NP_001159434.1	Q9BQ52-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELAC2	ENST00000338034.9	TSL:1 MANE Select	c.1560A>G	p.Thr520Thr	synonymous	Exon 17 of 24	ENSP00000337445.4	Q9BQ52-1
	ELAC2	ENST00000923774.1		c.1662A>G	p.Thr554Thr	synonymous	Exon 18 of 25	ENSP00000593833.1
	ELAC2	ENST00000860253.1		c.1584A>G	p.Thr528Thr	synonymous	Exon 18 of 25	ENSP00000530312.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40637 AN: 151840 Hom.: 5682 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.0301

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.275

GnomAD2 exomes AF: 0.272 AC: 68113 AN: 250592 AF XY: 0.276

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.254

Gnomad ASJ exome AF: 0.367

Gnomad EAS exome AF: 0.0342

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.308

GnomAD4 exome AF: 0.290 AC: 423972 AN: 1461478 Hom.: 63634 Cov.: 47 AF XY: 0.291 AC XY: 211294 AN XY: 727024

African (AFR) AF: 0.223 AC: 7477 AN: 33478

American (AMR) AF: 0.256 AC: 11440 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 9714 AN: 26128

East Asian (EAS) AF: 0.0311 AC: 1235 AN: 39698

South Asian (SAS) AF: 0.285 AC: 24612 AN: 86248

European-Finnish (FIN) AF: 0.316 AC: 16849 AN: 53266

Middle Eastern (MID) AF: 0.340 AC: 1958 AN: 5766

European-Non Finnish (NFE) AF: 0.300 AC: 333434 AN: 1111836

Other (OTH) AF: 0.286 AC: 17253 AN: 60374

GnomAD4 genome AF: 0.268 AC: 40663 AN: 151958 Hom.: 5692 Cov.: 32 AF XY: 0.266 AC XY: 19738 AN XY: 74258

African (AFR) AF: 0.222 AC: 9211 AN: 41462

American (AMR) AF: 0.252 AC: 3845 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3470

East Asian (EAS) AF: 0.0300 AC: 154 AN: 5140

South Asian (SAS) AF: 0.269 AC: 1292 AN: 4804

European-Finnish (FIN) AF: 0.312 AC: 3291 AN: 10552

Middle Eastern (MID) AF: 0.331 AC: 96 AN: 290

European-Non Finnish (NFE) AF: 0.302 AC: 20505 AN: 67954

Other (OTH) AF: 0.272 AC: 572 AN: 2106

Alfa AF: 0.264 Hom.: 1767

Bravo AF: 0.260

Asia WGS AF: 0.141 AC: 494 AN: 3478

EpiCase AF: 0.303

EpiControl AF: 0.298

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Combined oxidative phosphorylation defect type 17 (2)
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Prostate cancer, hereditary, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.12
DANN	Benign	0.61
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs11545302; hg19: chr17-12899963; COSMIC: COSV62032597; COSMIC: COSV62032597;