Genetic Variant PTCD3:c.*925T>C (chr2-86138484-T-C) – 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.*925T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,088 control chromosomes in the GnomAD database, including 12,900 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 0.37 ( 12897 hom., cov: 31)

Exomes 𝑓: 0.43 ( 3 hom. )

Consequence

PTCD3
NM_017952.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.123

Publications

22 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=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCD3	NM_017952.6 link	c.*925T>C		3_prime_UTR_variant	Exon 24 of 24	ENST00000254630.12	NP_060422.4	Q96EY7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCD3	ENST00000254630.12 link	c.*925T>C		3_prime_UTR_variant	Exon 24 of 24	1	NM_017952.6	ENSP00000254630.7		Q96EY7-1

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56391

AN:

151942

Hom.:

12902

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.567

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.472

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.395

GnomAD4 exome

AF:

0.429

AC:

AN:

Hom.:

Cov.:

AF XY:

0.417

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.389

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.371

AC:

56372

AN:

152060

Hom.:

12897

Cov.:

AF XY:

0.369

AC XY:

27404

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.112

AC:

4669

AN:

41512

American (AMR)

AF:

0.397

AC:

6062

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.472

AC:

1638

AN:

3468

East Asian (EAS)

AF:

0.159

AC:

821

AN:

5166

South Asian (SAS)

AF:

0.373

AC:

1798

AN:

4820

European-Finnish (FIN)

AF:

0.487

AC:

5144

AN:

10562

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.512

AC:

34769

AN:

67952

Other (OTH)

AF:

0.394

AC:

830

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1568

3136

4703

6271

7839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.460

Hom.:

29368

Bravo

AF:

0.351

Asia WGS

AF:

0.264

AC:

920

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.2

(source)

DANN

Benign

0.57

PhyloP100

0.12

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over