Genetic Variant PTCD1:p.Leu697Leu (chr7-99419979-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015545.4(PTCD1):c.2091T>C(p.Leu697Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 1,614,212 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 47 hom. )

Consequence

PTCD1
NM_015545.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.231

Variant links:

Genes affected

PTCD1 (HGNC:22198): (pentatricopeptide repeat domain 1) This gene encodes a mitochondrial protein that binds leucine tRNAs and other mitochondrial RNAs and plays a role in the regulation of translation. Increased expression of this gene results in decreased mitochondrial leucine tRNA levels. Naturally occurring read-through transcription exists between upstream ATP5J2 (ATP synthase, H+ transporting, mitochondrial Fo complex, subunit F2) and this gene. [provided by RefSeq, Aug 2015]

PTCD1 links:

ATP5MF-PTCD1 (HGNC:38844): (ATP5MF-PTCD1 readthrough) This locus represents naturally occurring read-through transcription between the ATP5J2 (ATP synthase, H+ transporting, mitochondrial Fo complex, subunit F2) and PTCD1 (pentatricopeptide repeat domain 1) genes on chromosome 7. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ATP5MF-PTCD1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 7-99419979-A-G is Benign according to our data. Variant chr7-99419979-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2657720.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.231 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCD1	NM_015545.4 link	c.2091T>C	p.Leu697Leu	synonymous_variant	Exon 8 of 8	ENST00000292478.9	NP_056360.2	O75127A4D273
ATP5MF-PTCD1	NM_001198879.2 link	c.2238T>C	p.Leu746Leu	synonymous_variant	Exon 9 of 9		NP_001185808.1	G3V325B4DJ38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCD1	ENST00000292478.9 link	c.2091T>C	p.Leu697Leu	synonymous_variant	Exon 8 of 8	1	NM_015545.4	ENSP00000292478.5		O75127
ATP5MF-PTCD1	ENST00000413834.5 link	c.2238T>C	p.Leu746Leu	synonymous_variant	Exon 9 of 9	2		ENSP00000400168.1		G3V325

Frequencies

GnomAD3 genomes

AF:

0.00522

AC:

794

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00767

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00643

AC:

1617

AN:

251460

Hom.:

AF XY:

0.00675

AC XY:

917

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00266

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00503

Gnomad FIN exome

AF:

0.0104

Gnomad NFE exome

AF:

0.00899

Gnomad OTH exome

AF:

0.00684

GnomAD4 exome

AF:

0.00665

AC:

9724

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00675

AC XY:

4906

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.00417

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00454

Gnomad4 FIN exome

AF:

0.0121

Gnomad4 NFE exome

AF:

0.00723

Gnomad4 OTH exome

AF:

0.00551

GnomAD4 genome

AF:

0.00521

AC:

794

AN:

152330

Hom.:

Cov.:

AF XY:

0.00529

AC XY:

394

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00393

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.00767

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00669

Hom.:

Bravo

AF:

0.00476

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00867

EpiControl

AF:

0.00913

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PTCD1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.38

DANN

Benign

0.64

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