Genetic Variant NM_015545.4:c.1420T>C (chr7-99425112-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015545.4(PTCD1):c.1420T>C(p.Phe474Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000446 in 1,614,046 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 1 hom. )

Consequence

PTCD1
NM_015545.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.93

Publications

1 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015545.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTCD1	NM_015545.4	MANE Select	c.1420T>C	p.Phe474Leu	missense	Exon 6 of 8	NP_056360.2
	ATP5MF-PTCD1	NM_001198879.2		c.1567T>C	p.Phe523Leu	missense	Exon 7 of 9	NP_001185808.1	G3V325

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTCD1	ENST00000292478.9	TSL:1 MANE Select	c.1420T>C	p.Phe474Leu	missense	Exon 6 of 8	ENSP00000292478.5	O75127
ATP5MF-PTCD1	ENST00000413834.5	TSL:2	c.1567T>C	p.Phe523Leu	missense	Exon 7 of 9	ENSP00000400168.1	G3V325
PTCD1	ENST00000910801.1		c.1420T>C	p.Phe474Leu	missense	Exon 6 of 8	ENSP00000580860.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000359

AC:

AN:

250850

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00171

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53300

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111970

Other (OTH)

AF:

0.0000166

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41568

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000577

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.54

MetaSVM

Uncertain

-0.26

MutationAssessor

Pathogenic

3.0

PhyloP100

5.9

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.36

Sift

Benign

0.072

Sift4G

Uncertain

0.037

Polyphen

0.99

Vest4

0.82

MutPred

0.46

Gain of disorder (P = 0.0995)

MVP

0.69

MPC

0.50

ClinPred

0.86

GERP RS

5.7

Varity_R

0.39

gMVP

0.71

Mutation Taster

=60/40

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over