chr13-100368441-A-G

Variant names:

• chr13-100368441-A-G
• rs9518061
• NM_000282.4:c.1644-31A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000282.4(PCCA):​c.1644-31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 1,162,430 control chromosomes in the GnomAD database, including 311,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (34172 hom., cov: 31)
  • Exomes 𝑓: 0.73 (276942 hom.)
• Consequence: PCCA NM_000282.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.28
• Publications: 8 publications found

Genes affected

PCCA (HGNC:8653): (propionyl-CoA carboxylase subunit alpha) The protein encoded by this gene is the alpha subunit of the heterodimeric mitochondrial enzyme Propionyl-CoA carboxylase. PCCA encodes the biotin-binding region of this enzyme. Mutations in either PCCA or PCCB (encoding the beta subunit) lead to an enzyme deficiency resulting in propionic acidemia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

PCCA Gene-Disease associations (from GenCC):

• propionic acidemia

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 13-100368441-A-G is Benign according to our data. Variant chr13-100368441-A-G is described in ClinVar as Benign. ClinVar VariationId is 255734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000282.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCCA	NM_000282.4	MANE Select	c.1644-31A>G		intron	N/A	NP_000273.2
	PCCA	NM_001352605.2		c.1644-31A>G		intron	N/A	NP_001339534.1
	PCCA	NM_001127692.3		c.1566-31A>G		intron	N/A	NP_001121164.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCCA	ENST00000376285.6	TSL:1 MANE Select	c.1644-31A>G		intron	N/A	ENSP00000365462.1
	PCCA	ENST00000881637.1		c.1767-31A>G		intron	N/A	ENSP00000551696.1
	PCCA	ENST00000881640.1		c.1749-31A>G		intron	N/A	ENSP00000551699.1

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100222 AN: 151802 Hom.: 34171 Cov.: 31

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.709

GnomAD2 exomes AF: 0.677 AC: 164516 AN: 242874 AF XY: 0.681

Gnomad AFR exome AF: 0.506

Gnomad AMR exome AF: 0.615

Gnomad ASJ exome AF: 0.716

Gnomad EAS exome AF: 0.462

Gnomad FIN exome AF: 0.682

Gnomad NFE exome AF: 0.776

Gnomad OTH exome AF: 0.721

GnomAD4 exome AF: 0.734 AC: 742152 AN: 1010510 Hom.: 276942 Cov.: 14 AF XY: 0.729 AC XY: 381294 AN XY: 522740

African (AFR) AF: 0.509 AC: 12184 AN: 23960

American (AMR) AF: 0.618 AC: 26704 AN: 43210

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 16539 AN: 23162

East Asian (EAS) AF: 0.517 AC: 19052 AN: 36864

South Asian (SAS) AF: 0.575 AC: 42781 AN: 74418

European-Finnish (FIN) AF: 0.692 AC: 36653 AN: 52952

Middle Eastern (MID) AF: 0.764 AC: 3717 AN: 4862

European-Non Finnish (NFE) AF: 0.782 AC: 552459 AN: 706112

Other (OTH) AF: 0.713 AC: 32063 AN: 44970

GnomAD4 genome AF: 0.660 AC: 100254 AN: 151920 Hom.: 34172 Cov.: 31 AF XY: 0.653 AC XY: 48444 AN XY: 74200

African (AFR) AF: 0.503 AC: 20837 AN: 41420

American (AMR) AF: 0.660 AC: 10076 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2456 AN: 3470

East Asian (EAS) AF: 0.461 AC: 2377 AN: 5158

South Asian (SAS) AF: 0.544 AC: 2614 AN: 4804

European-Finnish (FIN) AF: 0.678 AC: 7148 AN: 10540

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52331 AN: 67958

Other (OTH) AF: 0.713 AC: 1503 AN: 2108

Alfa AF: 0.692 Hom.: 4811

Bravo AF: 0.655

Asia WGS AF: 0.482 AC: 1672 AN: 3466

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	Propionic acidemia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.69
PhyloP100		2.3
PromoterAI		-0.0084	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9518061; hg19: chr13-101020695; COSMIC: COSV66191573; COSMIC: COSV66191573;