5-134959056-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_032151.5(PCBD2):​c.233C>T​(p.Ser78Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. S78C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PCBD2
NM_032151.5 missense

Scores

12
6
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.88
Variant links:
Genes affected
PCBD2 (HGNC:24474): (pterin-4 alpha-carbinolamine dehydratase 2) Predicted to enable 4-alpha-hydroxytetrahydrobiopterin dehydratase activity. Involved in positive regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.899

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCBD2NM_032151.5 linkc.233C>T p.Ser78Phe missense_variant Exon 3 of 4 ENST00000254908.11 NP_115527.3 Q9H0N5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCBD2ENST00000254908.11 linkc.233C>T p.Ser78Phe missense_variant Exon 3 of 4 1 NM_032151.5 ENSP00000254908.6 Q9H0N5
PCBD2ENST00000512783.5 linkc.233C>T p.Ser78Phe missense_variant Exon 3 of 5 1 ENSP00000421544.1 Q9H0N5
PCBD2ENST00000504352.1 linkn.200C>T non_coding_transcript_exon_variant Exon 3 of 8 5 ENSP00000426161.1 H0YA52
PCBD2ENST00000510013.1 linkn.322C>T non_coding_transcript_exon_variant Exon 3 of 3 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.84
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.80
D;D
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.82
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.86
.;D
M_CAP
Pathogenic
0.32
D
MetaRNN
Pathogenic
0.90
D;D
MetaSVM
Pathogenic
0.88
D
MutationAssessor
Pathogenic
2.9
M;M
PrimateAI
Uncertain
0.79
T
PROVEAN
Uncertain
-4.2
D;D
REVEL
Pathogenic
0.80
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.83
P;P
Vest4
0.76
MutPred
0.63
Loss of disorder (P = 0.0657);Loss of disorder (P = 0.0657);
MVP
0.96
MPC
0.80
ClinPred
1.0
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.78
gMVP
0.66

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: rs1273247512; hg19: chr5-134294746; API