Variant 3-57556446-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_177966.7(PDE12):c.67C>T(p.Arg23Trp) variant causes a missense change. The variant allele was found at a frequency of 0.441 in 1,611,968 control chromosomes in the GnomAD database, including 160,698 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.39 ( 12676 hom., cov: 34)

Exomes 𝑓: 0.45 ( 148022 hom. )

Consequence

PDE12
NM_177966.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.55

Variant links:

Genes affected

PDE12 (HGNC:25386): (phosphodiesterase 12) Enables 3'-5'-exoribonuclease activity. Involved in several processes, including RNA metabolic process; cellular response to cytokine stimulus; and regulation of mitochondrial mRNA stability. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Apr 2022]

PDE12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.518628E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE12	NM_177966.7 linkuse as main transcript	c.67C>T	p.Arg23Trp	missense_variant	1/3	ENST00000311180.9	NP_808881.3	Q6L8Q7-1
PDE12	NM_001322176.2 linkuse as main transcript	c.67C>T	p.Arg23Trp	missense_variant	1/3		NP_001309105.1
PDE12	NM_001322177.2 linkuse as main transcript	c.67C>T	p.Arg23Trp	missense_variant	1/2		NP_001309106.1	F6T1Q0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE12	ENST00000311180.9 linkuse as main transcript	c.67C>T	p.Arg23Trp	missense_variant	1/3	1	NM_177966.7	ENSP00000309142.7		Q6L8Q7-1
PDE12	ENST00000487257.1 linkuse as main transcript	c.67C>T	p.Arg23Trp	missense_variant	1/2	1		ENSP00000420626.1		F6T1Q0

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58736

AN:

152120

Hom.:

12677

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.556

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.560

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.563

Gnomad FIN

AF:

0.492

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.441

Gnomad OTH

AF:

0.423

GnomAD3 exomes

AF:

0.455

AC:

111696

AN:

245604

Hom.:

26346

AF XY:

0.466

AC XY:

62221

AN XY:

133566

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.442

Gnomad ASJ exome

AF:

0.574

Gnomad EAS exome

AF:

0.445

Gnomad SAS exome

AF:

0.555

Gnomad FIN exome

AF:

0.490

Gnomad NFE exome

AF:

0.452

Gnomad OTH exome

AF:

0.475

GnomAD4 exome

AF:

0.446

AC:

651409

AN:

1459730

Hom.:

148022

Cov.:

AF XY:

0.451

AC XY:

327727

AN XY:

726116

show subpopulations

Gnomad4 AFR exome

AF:

0.183

Gnomad4 AMR exome

AF:

0.444

Gnomad4 ASJ exome

AF:

0.570

Gnomad4 EAS exome

AF:

0.475

Gnomad4 SAS exome

AF:

0.555

Gnomad4 FIN exome

AF:

0.486

Gnomad4 NFE exome

AF:

0.439

Gnomad4 OTH exome

AF:

0.453

GnomAD4 genome

AF:

0.386

AC:

58742

AN:

152238

Hom.:

12676

Cov.:

AF XY:

0.394

AC XY:

29348

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.464

Gnomad4 ASJ

AF:

0.560

Gnomad4 EAS

AF:

0.442

Gnomad4 SAS

AF:

0.564

Gnomad4 FIN

AF:

0.492

Gnomad4 NFE

AF:

0.441

Gnomad4 OTH

AF:

0.427

Alfa

AF:

0.435

Hom.:

8090

Bravo

AF:

0.369

TwinsUK

AF:

0.431

AC:

1598

ALSPAC

AF:

0.426

AC:

1640

ESP6500AA

AF:

0.183

AC:

803

ESP6500EA

AF:

0.441

AC:

3778

ExAC

AF:

0.447

AC:

54203

Asia WGS

AF:

0.508

AC:

1766

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.72

T;T

MetaRNN

Benign

0.00045

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

.;L

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.70

N;N

REVEL

Benign

0.075

Sift

Benign

0.059

T;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.99

D;P

Vest4

0.093

ClinPred

0.083

GERP RS

3.7

Varity_R

0.19

gMVP

0.54

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over