rs150504114

Positions:

chr7-99434936-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015545.4(PTCD1):c.307C>T(p.Arg103Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0114 in 1,614,224 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 9 hom., cov: 32)

Exomes 𝑓: 0.012 ( 120 hom. )

Consequence

PTCD1
NM_015545.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.69

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:):

ATP5MF-PTCD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010560513).

BP6

Variant 7-99434936-G-A is Benign according to our data. Variant chr7-99434936-G-A is described in ClinVar as [Benign]. Clinvar id is 424616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00874 (1331/152330) while in subpopulation AMR AF= 0.0175 (268/15294). AF 95% confidence interval is 0.0158. There are 9 homozygotes in gnomad4. There are 611 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTCD1	NM_015545.4 linkuse as main transcript	c.307C>T	p.Arg103Cys	missense_variant	2/8	ENST00000292478.9	NP_056360.2
ATP5MF-PTCD1	NM_001198879.2 linkuse as main transcript	c.454C>T	p.Arg152Cys	missense_variant	3/9		NP_001185808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTCD1	ENST00000292478.9 linkuse as main transcript	c.307C>T	p.Arg103Cys	missense_variant	2/8	1	NM_015545.4	ENSP00000292478	P1

Frequencies

GnomAD3 genomes

AF:

0.00874

AC:

1331

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00258

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0175

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00869

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.00956

AC:

2405

AN:

251494

Hom.:

AF XY:

0.0101

AC XY:

1371

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.0131

Gnomad ASJ exome

AF:

0.0154

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.00973

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.0119

Gnomad OTH exome

AF:

0.0145

GnomAD4 exome

AF:

0.0116

AC:

17020

AN:

1461894

Hom.:

120

Cov.:

AF XY:

0.0118

AC XY:

8574

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00266

Gnomad4 AMR exome

AF:

0.0141

Gnomad4 ASJ exome

AF:

0.0176

Gnomad4 EAS exome

AF:

0.000831

Gnomad4 SAS exome

AF:

0.00974

Gnomad4 FIN exome

AF:

0.000655

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.0122

GnomAD4 genome

AF:

0.00874

AC:

1331

AN:

152330

Hom.:

Cov.:

AF XY:

0.00820

AC XY:

611

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00257

Gnomad4 AMR

AF:

0.0175

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00849

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.00970

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0141

AC:

121

ExAC

AF:

0.00927

AC:

1126

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0143

EpiControl

AF:

0.0140

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Kabuki syndrome 1

Benign:1

Benign, criteria provided, single submitter

research

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

The heterozygous p.Arg103Cys variant, sometimes called p.Arg152Cys due to a difference in cDNA numbering, in PTCD1 has been identified in an individual with Complex I deficiency (PMID: 20818383), and has been identified in >1% of European (non-Finnish) chromosomes and 13 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as benign for autosomal recessive Complex I deficiency. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

T;.;.;.;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.68

T;T;T;T;T

MetaRNN

Benign

0.011

T;T;T;T;T

MetaSVM

Uncertain

0.0085

MutationAssessor

Benign

2.0

M;.;.;.;.

MutationTaster

Benign

0.61

N;N;N

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-3.9

D;D;D;D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0040

D;D;D;D;D

Sift4G

Uncertain

0.0020

D;D;.;D;D

Polyphen

1.0

D;.;.;.;D

Vest4

0.28

MVP

0.97

MPC

0.43

ClinPred

0.025

GERP RS

6.0

Varity_R

0.092

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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