Variant chr5-134960664-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032151.5(PCBD2):c.376G>C(p.Ala126Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,611,138 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PCBD2
NM_032151.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74

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]

PCBD2 links:

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/exons	MANE	Protein	UniProt
PCBD2	NM_032151.5 linkuse as main transcript	c.376G>C	p.Ala126Pro	missense_variant	4/4	ENST00000254908.11	NP_115527.3	Q9H0N5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PCBD2	ENST00000254908.11 linkuse as main transcript	c.376G>C	p.Ala126Pro	missense_variant	4/4	1	NM_032151.5	ENSP00000254908.6	Q9H0N5
PCBD2	ENST00000512783.5 linkuse as main transcript	c.376G>C	p.Ala126Pro	missense_variant	4/5	1		ENSP00000421544.1	Q9H0N5
PCBD2	ENST00000504352.1 linkuse as main transcript	n.343G>C		non_coding_transcript_exon_variant	4/8	5		ENSP00000426161.1	H0YA52

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

249082

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000390

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:

0.00000206

AC:

AN:

1458960

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

725970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

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

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.376G>C (p.A126P) alteration is located in exon 4 (coding exon 4) of the PCBD2 gene. This alteration results from a G to C substitution at nucleotide position 376, causing the alanine (A) at amino acid position 126 to be replaced by a proline (P). 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

0.94

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.81

D;D

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

.;D

M_CAP

Uncertain

0.21

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Pathogenic

0.90

MutationAssessor

Pathogenic

3.1

M;M

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.5

D;D

REVEL

Uncertain

0.61

Sift

Benign

0.042

D;D

Sift4G

Benign

0.090

T;T

Polyphen

0.99

D;D

Vest4

0.49

MutPred

0.72

Loss of MoRF binding (P = 0.0345);Loss of MoRF binding (P = 0.0345);

MVP

0.83

MPC

0.89

ClinPred

0.68

GERP RS

5.1

Varity_R

0.84

gMVP

0.82

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over