dbSNP rs16843829: PCCB:c.372+31T>C (chr3-136256654-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000532.5(PCCB):c.372+31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00601 in 1,449,700 control chromosomes in the GnomAD database, including 663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 75 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 588 hom. )

Consequence

PCCB
NM_000532.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.121

Publications

4 publications found

Variant links:

Genes affected

PCCB (HGNC:8654): (propionyl-CoA carboxylase subunit beta) The protein encoded by this gene is a subunit of the propionyl-CoA carboxylase (PCC) enzyme, which is involved in the catabolism of propionyl-CoA. PCC is a mitochondrial enzyme that probably acts as a dodecamer of six alpha subunits and six beta subunits. This gene encodes the beta subunit of PCC. Defects in this gene are a cause of propionic acidemia type II (PA-2). Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

PCCB Gene-Disease associations (from GenCC):

propionic acidemia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Myriad Women’s Health, Orphanet

PCCB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 3-136256654-T-C is Benign according to our data. Variant chr3-136256654-T-C is described in ClinVar as Benign. ClinVar VariationId is 256374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PCCB	NM_000532.5 link	c.372+31T>C	intron_variant	Intron 3 of 14	ENST00000251654.9	NP_000523.2
PCCB	NM_001178014.2 link	c.372+31T>C	intron_variant	Intron 3 of 15		NP_001171485.1
PCCB	XM_011512873.2 link	c.372+31T>C	intron_variant	Intron 3 of 10		XP_011511175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCCB	ENST00000251654.9 link	c.372+31T>C		intron_variant	Intron 3 of 14	1	NM_000532.5	ENSP00000251654.4

Frequencies

GnomAD3 genomes

AF:

0.00705

AC:

1073

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.00475

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.00622

GnomAD2 exomes

AF:

0.0148

AC:

3725

AN:

251186

AF XY:

0.0135

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00328

Gnomad EAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.000255

Gnomad OTH exome

AF:

0.00751

GnomAD4 exome

AF:

0.00589

AC:

7640

AN:

1297368

Hom.:

588

Cov.:

AF XY:

0.00557

AC XY:

3644

AN XY:

654008

show subpopulations

African (AFR)

AF:

0.000858

AC:

AN:

30286

American (AMR)

AF:

0.00209

AC:

AN:

44520

Ashkenazi Jewish (ASJ)

AF:

0.00287

AC:

AN:

25090

East Asian (EAS)

AF:

0.158

AC:

6144

AN:

38934

South Asian (SAS)

AF:

0.00286

AC:

237

AN:

83004

European-Finnish (FIN)

AF:

0.000319

AC:

AN:

53334

Middle Eastern (MID)

AF:

0.00147

AC:

AN:

5440

European-Non Finnish (NFE)

AF:

0.000160

AC:

154

AN:

961794

Other (OTH)

AF:

0.0162

AC:

889

AN:

54966

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

348

696

1043

1391

1739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00706

AC:

1075

AN:

152332

Hom.:

Cov.:

AF XY:

0.00758

AC XY:

565

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00154

AC:

AN:

41572

American (AMR)

AF:

0.00353

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3470

East Asian (EAS)

AF:

0.169

AC:

877

AN:

5182

South Asian (SAS)

AF:

0.00455

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68036

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

146

195

244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00276

Hom.:

Bravo

AF:

0.00845

Asia WGS

AF:

0.0790

AC:

272

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jul 27, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over