dbSNP rs140335642: ELAC2:p.Pro493Pro (chr17-12998453-C-G) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_018127.7(ELAC2):c.1479G>C(p.Pro493Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,614,176 control chromosomes in the GnomAD database, including 28 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. P493P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0084 ( 14 hom., cov: 33)

Exomes 𝑓: 0.00085 ( 14 hom. )

Consequence

ELAC2
NM_018127.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.14

Publications

2 publications found

Variant links:

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

ELAC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.068).

BP6

Variant 17-12998453-C-G is Benign according to our data. Variant chr17-12998453-C-G is described in ClinVar as Benign. ClinVar VariationId is 241270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.14 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0084 (1280/152304) while in subpopulation AFR AF = 0.0285 (1186/41554). AF 95% confidence interval is 0.0272. There are 14 homozygotes in GnomAd4. There are 652 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELAC2	NM_018127.7	MANE Select	c.1479G>C	p.Pro493Pro	synonymous	Exon 16 of 24	NP_060597.4
ELAC2	NM_173717.2		c.1476G>C	p.Pro492Pro	synonymous	Exon 16 of 24	NP_776065.1
ELAC2	NM_001165962.2		c.1359G>C	p.Pro453Pro	synonymous	Exon 15 of 23	NP_001159434.1	Q9BQ52-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELAC2	ENST00000338034.9	TSL:1 MANE Select	c.1479G>C	p.Pro493Pro	synonymous	Exon 16 of 24	ENSP00000337445.4	Q9BQ52-1
ELAC2	ENST00000446899.5	TSL:5	c.816G>C	p.Pro272Pro	synonymous	Exon 10 of 10	ENSP00000406192.1	H7C2I4
ELAC2	ENST00000923774.1		c.1581G>C	p.Pro527Pro	synonymous	Exon 17 of 25	ENSP00000593833.1

Frequencies

GnomAD3 genomes

AF:

0.00837

AC:

1274

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00209

AC:

525

AN:

251478

AF XY:

0.00147

show subpopulations

Gnomad AFR exome

AF:

0.0278

Gnomad AMR exome

AF:

0.00171

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000615

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.000853

AC:

1247

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

527

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0286

AC:

957

AN:

33476

American (AMR)

AF:

0.00201

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00433

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000324

AC:

AN:

1111996

Other (OTH)

AF:

0.00220

AC:

133

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

142

214

285

356

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00840

AC:

1280

AN:

152304

Hom.:

Cov.:

AF XY:

0.00875

AC XY:

652

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0285

AC:

1186

AN:

41554

American (AMR)

AF:

0.00405

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68038

Other (OTH)

AF:

0.00993

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

130

195

260

325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000605

Hom.:

Bravo

AF:

0.00980

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Combined oxidative phosphorylation defect type 17 (1)

not provided (1)

not specified (1)

Prostate cancer, hereditary, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.99

(source)

DANN

Benign

0.54

PhyloP100

-3.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over