2-86106252-C-G

Variant summary

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

The NM_017952.6(PTCD3):​c.5C>G​(p.Ala2Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,502 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2V) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

PTCD3
NM_017952.6 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.99
Variant links:
Genes affected
PTCD3 (HGNC:24717): (pentatricopeptide repeat domain 3) Enables rRNA binding activity and ribosomal small subunit binding activity. Involved in mitochondrial translation. Located in several cellular components, including cytosol; mitochondrion; and nucleoplasm. Implicated in combined oxidative phosphorylation deficiency 51. [provided by Alliance of Genome Resources, Apr 2022]
POLR1A (HGNC:17264): (RNA polymerase I subunit A) The protein encoded by this gene is the largest subunit of the RNA polymerase I complex. The encoded protein represents the catalytic subunit of the complex, which transcribes DNA into ribosomal RNA precursors. Defects in this gene are a cause of the Cincinnati type of acrofacial dysostosis. [provided by RefSeq, May 2016]

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
PTCD3NM_017952.6 linkc.5C>G p.Ala2Gly missense_variant Exon 1 of 24 ENST00000254630.12 NP_060422.4 Q96EY7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTCD3ENST00000254630.12 linkc.5C>G p.Ala2Gly missense_variant Exon 1 of 24 1 NM_017952.6 ENSP00000254630.7 Q96EY7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251368
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135888
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
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:
6.84e-7
AC:
1
AN:
1461502
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727074
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Uncertain
0.040
T
BayesDel_noAF
Benign
-0.10
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0090
T;T;T
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.42
T;T;T
M_CAP
Benign
0.030
D
MetaRNN
Uncertain
0.64
D;D;D
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Uncertain
2.3
M;.;.
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.71
N;N;.
REVEL
Benign
0.17
Sift
Pathogenic
0.0
D;D;.
Sift4G
Benign
0.061
T;D;D
Polyphen
1.0
D;.;.
Vest4
0.48
MutPred
0.28
Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);
MVP
0.72
MPC
0.33
ClinPred
0.98
D
GERP RS
5.2
Varity_R
0.36
gMVP
0.60

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.

Other links and lift over

dbSNP: rs13393659; hg19: chr2-86333375; API