Variant rs9833162 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000532.5(PCCB):c.967-46A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,602,770 control chromosomes in the GnomAD database, including 92,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10861 hom., cov: 32)

Exomes 𝑓: 0.33 ( 81356 hom. )

Consequence

PCCB
NM_000532.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.882

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-136316895-A-G is Benign according to our data. Variant chr3-136316895-A-G is described in ClinVar as [Benign]. Clinvar id is 256376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
PCCB	NM_000532.5 linkuse as main transcript	c.967-46A>G	intron_variant	ENST00000251654.9	NP_000523.2
PCCB	NM_001178014.2 linkuse as main transcript	c.1027-46A>G	intron_variant		NP_001171485.1
PCCB	XM_011512873.2 linkuse as main transcript	c.967-46A>G	intron_variant		XP_011511175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCCB	ENST00000251654.9 linkuse as main transcript	c.967-46A>G		intron_variant		1	NM_000532.5	ENSP00000251654	P2	P05166-1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54738

AN:

151862

Hom.:

10847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.515

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.244

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.00638

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.335

GnomAD3 exomes

AF:

0.295

AC:

73976

AN:

250884

Hom.:

12676

AF XY:

0.299

AC XY:

40628

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.515

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.321

Gnomad EAS exome

AF:

0.00327

Gnomad SAS exome

AF:

0.333

Gnomad FIN exome

AF:

0.302

Gnomad NFE exome

AF:

0.340

Gnomad OTH exome

AF:

0.295

GnomAD4 exome

AF:

0.327

AC:

473777

AN:

1450790

Hom.:

81356

Cov.:

AF XY:

0.328

AC XY:

236998

AN XY:

722492

show subpopulations

Gnomad4 AFR exome

AF:

0.512

Gnomad4 AMR exome

AF:

0.165

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.00202

Gnomad4 SAS exome

AF:

0.338

Gnomad4 FIN exome

AF:

0.305

Gnomad4 NFE exome

AF:

0.340

Gnomad4 OTH exome

AF:

0.322

GnomAD4 genome

AF:

0.360

AC:

54780

AN:

151980

Hom.:

10861

Cov.:

AF XY:

0.353

AC XY:

26187

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.515

Gnomad4 AMR

AF:

0.244

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.00640

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.300

Gnomad4 NFE

AF:

0.337

Gnomad4 OTH

AF:

0.331

Alfa

AF:

0.338

Hom.:

4658

Bravo

AF:

0.360

Asia WGS

AF:

0.154

AC:

536

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Propionic acidemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

DANN

Benign

0.39

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