chr5-134959056-C-G

Position:

• chr5-134959056-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032151.5(PCBD2):​c.233C>G​(p.Ser78Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCBD2 NM_032151.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.88

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]

PCBD2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.813

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCBD2	NM_032151.5	c.233C>G	p.Ser78Cys	missense_variant	3/4	ENST00000254908.11	NP_115527.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCBD2	ENST00000254908.11	c.233C>G	p.Ser78Cys	missense_variant	3/4	1	NM_032151.5	ENSP00000254908.6
PCBD2	ENST00000512783.5	c.233C>G	p.Ser78Cys	missense_variant	3/5	1		ENSP00000421544.1
PCBD2	ENST00000504352.1	n.200C>G		non_coding_transcript_exon_variant	3/8	5		ENSP00000426161.1
PCBD2	ENST00000510013.1	n.322C>G		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.233C>G (p.S78C) alteration is located in exon 3 (coding exon 3) of the PCBD2 gene. This alteration results from a C to G substitution at nucleotide position 233, causing the serine (S) at amino acid position 78 to be replaced by a cysteine (C). 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	Benign	0.10
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.75	D;D
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Pathogenic	0.89	D
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0050	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.98	D;D
Vest4		0.62
MutPred		0.63		Loss of disorder (P = 0.0502);Loss of disorder (P = 0.0502);
MVP		0.97
MPC		0.27
ClinPred		0.97	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.38
gMVP		0.51

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

Other links and lift over

dbSNP: rs1273247512; hg19: chr5-134294746;