Genetic Variant NM_017952.6:c.1543+14T>G (chr2-86133450-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017952.6(PTCD3):c.1543+14T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 1,587,638 control chromosomes in the GnomAD database, including 2,173 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.

Frequency

Genomes: 𝑓 0.035 ( 230 hom., cov: 32)

Exomes 𝑓: 0.040 ( 1943 hom. )

Consequence

PTCD3
NM_017952.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.144

Publications

14 publications found

Variant links:

Genes affected

PTCD3 (HGNC:24717): (pentatricopeptide repeat domain 3) Enables rRNA binding activity and ribosomal small subunit binding activity. Involved in mitochondrial translation. Located in several cellular components, including cytosol; mitochondrion; and nucleoplasm. Implicated in combined oxidative phosphorylation deficiency 51. [provided by Alliance of Genome Resources, Apr 2022]

PTCD3 Gene-Disease associations (from GenCC):

combined oxidative phosphorylation deficiency 51
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

PTCD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017952.6. 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
	PTCD3	NM_017952.6	MANE Select	c.1543+14T>G		intron	N/A	NP_060422.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PTCD3	ENST00000254630.12	TSL:1 MANE Select	c.1543+14T>G	intron	N/A	ENSP00000254630.7	Q96EY7-1
PTCD3	ENST00000898160.1		c.1561+14T>G	intron	N/A	ENSP00000568219.1
PTCD3	ENST00000898158.1		c.1543+14T>G	intron	N/A	ENSP00000568217.1

Frequencies

GnomAD3 genomes

AF:

0.0350

AC:

5323

AN:

152232

Hom.:

230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0103

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0397

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.0267

Gnomad FIN

AF:

0.00706

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0393

Gnomad OTH

AF:

0.0468

GnomAD2 exomes

AF:

0.0446

AC:

11199

AN:

251010

AF XY:

0.0439

show subpopulations

Gnomad AFR exome

AF:

0.00824

Gnomad AMR exome

AF:

0.0244

Gnomad ASJ exome

AF:

0.0187

Gnomad EAS exome

AF:

0.234

Gnomad FIN exome

AF:

0.00801

Gnomad NFE exome

AF:

0.0409

Gnomad OTH exome

AF:

0.0404

GnomAD4 exome

AF:

0.0400

AC:

57349

AN:

1435288

Hom.:

1943

Cov.:

AF XY:

0.0396

AC XY:

28324

AN XY:

715486

show subpopulations

African (AFR)

AF:

0.00723

AC:

237

AN:

32766

American (AMR)

AF:

0.0252

AC:

1126

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.0186

AC:

482

AN:

25950

East Asian (EAS)

AF:

0.213

AC:

8421

AN:

39560

South Asian (SAS)

AF:

0.0226

AC:

1937

AN:

85632

European-Finnish (FIN)

AF:

0.00839

AC:

448

AN:

53402

Middle Eastern (MID)

AF:

0.0471

AC:

269

AN:

5716

European-Non Finnish (NFE)

AF:

0.0384

AC:

41804

AN:

1088090

Other (OTH)

AF:

0.0441

AC:

2625

AN:

59538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

2837

5673

8510

11346

14183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1598

3196

4794

6392

7990

<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:

0.0350

AC:

5334

AN:

152350

Hom.:

230

Cov.:

AF XY:

0.0350

AC XY:

2605

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0104

AC:

433

AN:

41584

American (AMR)

AF:

0.0397

AC:

607

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

3472

East Asian (EAS)

AF:

0.228

AC:

1182

AN:

5182

South Asian (SAS)

AF:

0.0269

AC:

130

AN:

4828

European-Finnish (FIN)

AF:

0.00706

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0393

AC:

2675

AN:

68038

Other (OTH)

AF:

0.0520

AC:

110

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

257

514

772

1029

1286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

204

272

340

<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:

0.0442

Hom.:

134

Bravo

AF:

0.0368

Asia WGS

AF:

0.118

AC:

412

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.5

(source)

DANN

Benign

0.30

PhyloP100

0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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