Variant chr2-86121556-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017952.6(PTCD3):c.616G>T(p.Asp206Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,610,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PTCD3
NM_017952.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10604915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCD3	NM_017952.6 linkuse as main transcript	c.616G>T	p.Asp206Tyr	missense_variant	8/24	ENST00000254630.12	NP_060422.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCD3	ENST00000254630.12 linkuse as main transcript	c.616G>T	p.Asp206Tyr	missense_variant	8/24	1	NM_017952.6	ENSP00000254630	P1	Q96EY7-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248622

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134328

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458318

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725382

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151928

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74156

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000480

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 28, 2024

The c.616G>T (p.D206Y) alteration is located in exon 8 (coding exon 8) of the PTCD3 gene. This alteration results from a G to T substitution at nucleotide position 616, causing the aspartic acid (D) at amino acid position 206 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.019

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.66

M_CAP

Benign

0.0090

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.028

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

0.036

Vest4

0.21

MutPred

0.37

Gain of helix (P = 0.0199);

MVP

0.18

MPC

0.064

ClinPred

0.14

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.090

gMVP

0.62

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over