NM_017952.6:c.413C>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP3BS1_Supporting

The NM_017952.6(PTCD3):c.413C>T(p.Pro138Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000132 in 1,074,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000080 ( 0 hom. )

Consequence

PTCD3
NM_017952.6 missense, splice_region

Scores

Splicing: ADA: 0.9914

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 6.06

Publications

2 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: Uncertain_significance. The variant received 0 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000447 (68/152132) while in subpopulation AFR AF = 0.00135 (56/41494). AF 95% confidence interval is 0.00107. There are 0 homozygotes in GnomAd4. There are 29 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.413C>T	p.Pro138Leu	missense splice_region	Exon 6 of 24	NP_060422.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTCD3	ENST00000254630.12	TSL:1 MANE Select	c.413C>T	p.Pro138Leu	missense splice_region	Exon 6 of 24	ENSP00000254630.7	Q96EY7-1
PTCD3	ENST00000938579.1		c.413C>T	p.Pro138Leu	missense	Exon 6 of 23	ENSP00000608638.1
PTCD3	ENST00000898160.1		c.431C>T	p.Pro144Leu	missense splice_region	Exon 6 of 24	ENSP00000568219.1

Frequencies

GnomAD3 genomes

AF:

0.000447

AC:

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000156

AC:

AN:

243184

AF XY:

0.0000986

show subpopulations

Gnomad AFR exome

AF:

0.00102

Gnomad AMR exome

AF:

0.000216

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000560

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000360

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000803

AC:

AN:

921976

Hom.:

Cov.:

AF XY:

0.0000645

AC XY:

AN XY:

480922

show subpopulations

African (AFR)

AF:

0.00114

AC:

AN:

22712

American (AMR)

AF:

0.000167

AC:

AN:

41900

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22484

East Asian (EAS)

AF:

0.000161

AC:

AN:

37184

South Asian (SAS)

AF:

0.0000137

AC:

AN:

73144

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4702

European-Non Finnish (NFE)

AF:

0.0000416

AC:

AN:

624560

Other (OTH)

AF:

0.000165

AC:

AN:

42308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000447

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41494

American (AMR)

AF:

0.000196

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68008

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000179

Hom.:

Bravo

AF:

0.000495

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000198

AC:

Asia WGS

AF:

0.000867

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

M_CAP

Benign

0.036

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

PhyloP100

6.1

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-5.2

REVEL

Benign

0.17

Sift

Uncertain

0.0080

Sift4G

Pathogenic

0.0

Polyphen

0.84

Vest4

0.75

MVP

0.32

MPC

0.078

ClinPred

0.065

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.46

gMVP

0.77

Mutation Taster

=39/61

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.83

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