rs140492017

Variant names:

• chr13-100530318-C-CA
• rs140492017
• NM_000282.4:c.*158dupA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000282.4(PCCA):​c.*158dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00632 in 693,280 control chromosomes in the GnomAD database, including 131 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (87 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (44 hom.)
• Consequence: PCCA NM_000282.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.39
• Publications: 0 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]

GGACT (HGNC:25100): (gamma-glutamylamine cyclotransferase) The protein encoded by this gene aids in the proteolytic degradation of crosslinked fibrin by breaking down isodipeptide L-gamma-glutamyl-L-epsilon-lysine, a byproduct of fibrin degradation. The reaction catalyzed by the encoded gamma-glutamylaminecyclotransferase produces 5-oxo-L-proline and a free alkylamine. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Aug 2010]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 13-100530318-C-CA is Benign according to our data. Variant chr13-100530318-C-CA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 310855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0648 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.*158dupA		3_prime_UTR	Exon 24 of 24	NP_000273.2	P05165-1
	GGACT	NM_001195087.2	MANE Select	c.*1811dupT		3_prime_UTR	Exon 3 of 3	NP_001182016.1	Q9BVM4
	PCCA	NM_001352605.2		c.*158dupA		3_prime_UTR	Exon 23 of 23	NP_001339534.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCCA	ENST00000376285.6	TSL:1 MANE Select	c.*158dupA		3_prime_UTR	Exon 24 of 24	ENSP00000365462.1	P05165-1
	GGACT	ENST00000683975.1	MANE Select	c.*1811dupT		3_prime_UTR	Exon 3 of 3	ENSP00000508020.1	Q9BVM4
	GGACT	ENST00000455100.2	TSL:1	c.*1811dupT		3_prime_UTR	Exon 2 of 2	ENSP00000410449.1	Q9BVM4

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2974 AN: 152102 Hom.: 85 Cov.: 33

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00950

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.0182

GnomAD4 exome AF: 0.00259 AC: 1399 AN: 541060 Hom.: 44 Cov.: 6 AF XY: 0.00214 AC XY: 619 AN XY: 289234

African (AFR) AF: 0.0649 AC: 952 AN: 14668

American (AMR) AF: 0.00508 AC: 155 AN: 30498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18692

East Asian (EAS) AF: 0.00 AC: 0 AN: 31708

South Asian (SAS) AF: 0.000294 AC: 17 AN: 57862

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40594

Middle Eastern (MID) AF: 0.00314 AC: 11 AN: 3502

European-Non Finnish (NFE) AF: 0.000264 AC: 83 AN: 313986

Other (OTH) AF: 0.00613 AC: 181 AN: 29550

GnomAD4 genome AF: 0.0196 AC: 2984 AN: 152220 Hom.: 87 Cov.: 33 AF XY: 0.0189 AC XY: 1409 AN XY: 74416

African (AFR) AF: 0.0668 AC: 2775 AN: 41520

American (AMR) AF: 0.00949 AC: 145 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68026

Other (OTH) AF: 0.0180 AC: 38 AN: 2110

Alfa AF: 0.0144 Hom.: 10

Bravo AF: 0.0223

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Propionic acidemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs140492017; hg19: chr13-101182572;