dbSNP rs771327394: PTCD2:p.Tyr46Phe (chr5-72322181-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024754.5(PTCD2):c.137A>T(p.Tyr46Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000022 in 1,411,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

PTCD2
NM_024754.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.41

Publications

0 publications found

Variant links:

Genes affected

PTCD2 (HGNC:25734): (pentatricopeptide repeat domain 2) Enables RNA binding activity. Predicted to be involved in mitochondrion organization and regulation of mRNA processing. Predicted to act upstream of or within animal organ development; muscle cell development; and regulation of gene expression. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

PTCD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4020797).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024754.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTCD2	NM_024754.5	MANE Select	c.137A>T	p.Tyr46Phe	missense	Exon 2 of 10	NP_079030.3
PTCD2	NM_001284403.2		c.137A>T	p.Tyr46Phe	missense	Exon 2 of 7	NP_001271332.1	Q8WV60-3
PTCD2	NM_001284404.2		c.-183A>T		5_prime_UTR	Exon 2 of 8	NP_001271333.1	Q8WV60-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTCD2	ENST00000380639.10	TSL:5 MANE Select	c.137A>T	p.Tyr46Phe	missense	Exon 2 of 10	ENSP00000370013.4	Q8WV60-1
PTCD2	ENST00000308077.9	TSL:1	n.137A>T		non_coding_transcript_exon	Exon 2 of 11	ENSP00000308948.5	Q8WV60-1
PTCD2	ENST00000866840.1		c.137A>T	p.Tyr46Phe	missense	Exon 2 of 9	ENSP00000536899.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000203

AC:

AN:

245774

AF XY:

0.0000150

show subpopulations

Gnomad AFR exome

AF:

0.0000649

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1411204

Hom.:

Cov.:

AF XY:

0.0000184

AC XY:

AN XY:

705022

show subpopulations

African (AFR)

AF:

0.0000310

AC:

AN:

32210

American (AMR)

AF:

0.00

AC:

AN:

43420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25744

East Asian (EAS)

AF:

0.00

AC:

AN:

39370

South Asian (SAS)

AF:

0.00

AC:

AN:

84336

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5480

European-Non Finnish (NFE)

AF:

0.0000271

AC:

AN:

1068834

Other (OTH)

AF:

0.0000171

AC:

AN:

58644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

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

Cov.:

Alfa

AF:

0.0000312

Hom.:

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00000828

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Benign

0.14

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0085

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.6

PhyloP100

5.4

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.8

REVEL

Benign

0.22

Sift

Benign

0.11

Sift4G

Benign

0.13

Polyphen

1.0

Vest4

0.43

MutPred

0.64

Loss of catalytic residue at L41 (P = 0.0601)

MVP

0.63

MPC

0.51

ClinPred

0.60

GERP RS

5.8

Varity_R

0.14

gMVP

0.26

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over