Variant 2-86111154-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017952.6(PTCD3):c.236A>G(p.Asn79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,612,978 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 2 hom. )

Consequence

PTCD3
NM_017952.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044454575).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCD3	NM_017952.6 linkuse as main transcript	c.236A>G	p.Asn79Ser	missense_variant	4/24	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.236A>G	p.Asn79Ser	missense_variant	4/24	1	NM_017952.6	ENSP00000254630	P1	Q96EY7-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000955

AC:

AN:

251216

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.0000616

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:

0.000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000787

AC:

115

AN:

1460884

Hom.:

Cov.:

AF XY:

0.0000936

AC XY:

AN XY:

726836

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

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:

0.0000187

Gnomad4 NFE exome

AF:

0.0000981

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000145

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000245

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

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

Dec 17, 2023

The c.236A>G (p.N79S) alteration is located in exon 4 (coding exon 4) of the PTCD3 gene. This alteration results from a A to G substitution at nucleotide position 236, causing the asparagine (N) at amino acid position 79 to be replaced by a serine (S). 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

0.065

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0092

T;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.35

N;N

REVEL

Benign

0.086

Sift

Benign

0.82

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.0030

B;.

Vest4

0.21

MVP

0.085

MPC

0.045

ClinPred

0.022

GERP RS

-0.076

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.015

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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