5-72331308-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001284405.2(PTCD2):​c.-91C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000304 in 1,613,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

PTCD2
NM_001284405.2 5_prime_UTR_premature_start_codon_gain

Scores

4
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.12
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTCD2NM_024754.5 linkc.401C>T p.Pro134Leu missense_variant Exon 4 of 10 ENST00000380639.10 NP_079030.3 Q8WV60-1A0A024RAM6B3KPU6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTCD2ENST00000380639.10 linkc.401C>T p.Pro134Leu missense_variant Exon 4 of 10 5 NM_024754.5 ENSP00000370013.4 Q8WV60-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152042
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000111
AC:
28
AN:
251484
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00152
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000287
AC:
42
AN:
1461704
Hom.:
0
Cov.:
30
AF XY:
0.0000330
AC XY:
24
AN XY:
727152
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152160
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000156
Hom.:
0
Bravo
AF:
0.0000491
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 08, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.401C>T (p.P134L) alteration is located in exon 4 (coding exon 4) of the PTCD2 gene. This alteration results from a C to T substitution at nucleotide position 401, causing the proline (P) at amino acid position 134 to be replaced by a leucine (L). 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
Pathogenic
0.57
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.61
D
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.97
D
M_CAP
Benign
0.039
D
MetaRNN
Uncertain
0.61
D
MetaSVM
Benign
-0.48
T
MutationAssessor
Pathogenic
3.0
M
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-7.8
D
REVEL
Uncertain
0.39
Sift
Uncertain
0.0030
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.94
MVP
0.68
MPC
0.57
ClinPred
0.72
D
GERP RS
5.3
Varity_R
0.62
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs182906186; hg19: chr5-71627135; COSMIC: COSV57337912; COSMIC: COSV57337912; API