rs41281124

Variant names:

• chr13-100530356-C-G
• rs41281124
• NM_000282.4:c.*190C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-100530356-C-G
• chr13-100530356-C-T
• chr13-100530356-C-A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS1

The NM_000282.4(PCCA):​c.*190C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 645,374 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (1 hom.)
• Consequence: PCCA NM_000282.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00127 (193/152326) while in subpopulation NFE AF = 0.00231 (157/68028). AF 95% confidence interval is 0.00201. There are 1 homozygotes in GnomAd4. There are 94 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.*190C>G		3_prime_UTR	Exon 24 of 24	NP_000273.2	P05165-1
	GGACT	NM_001195087.2	MANE Select	c.*1774G>C		3_prime_UTR	Exon 3 of 3	NP_001182016.1	Q9BVM4
	PCCA	NM_001352605.2		c.*190C>G		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.*190C>G		3_prime_UTR	Exon 24 of 24	ENSP00000365462.1	P05165-1
	GGACT	ENST00000683975.1	MANE Select	c.*1774G>C		3_prime_UTR	Exon 3 of 3	ENSP00000508020.1	Q9BVM4
	GGACT	ENST00000455100.2	TSL:1	c.*1774G>C		3_prime_UTR	Exon 2 of 2	ENSP00000410449.1	Q9BVM4

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 193 AN: 152208 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00174 AC: 858 AN: 493048 Hom.: 1 Cov.: 4 AF XY: 0.00154 AC XY: 405 AN XY: 262442

African (AFR) AF: 0.000425 AC: 6 AN: 14124

American (AMR) AF: 0.000242 AC: 7 AN: 28876

Ashkenazi Jewish (ASJ) AF: 0.00215 AC: 35 AN: 16280

East Asian (EAS) AF: 0.00 AC: 0 AN: 31360

South Asian (SAS) AF: 0.00 AC: 0 AN: 50886

European-Finnish (FIN) AF: 0.00116 AC: 38 AN: 32834

Middle Eastern (MID) AF: 0.000397 AC: 1 AN: 2522

European-Non Finnish (NFE) AF: 0.00254 AC: 732 AN: 288304

Other (OTH) AF: 0.00140 AC: 39 AN: 27862

GnomAD4 genome AF: 0.00127 AC: 193 AN: 152326 Hom.: 1 Cov.: 33 AF XY: 0.00126 AC XY: 94 AN XY: 74488

African (AFR) AF: 0.000457 AC: 19 AN: 41582

American (AMR) AF: 0.000196 AC: 3 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10610

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

European-Non Finnish (NFE) AF: 0.00231 AC: 157 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000478 Hom.: 0

Bravo AF: 0.00113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Propionic acidemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		2.5
Mutation Taster		=100/0	polymorphism

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: rs41281124; hg19: chr13-101182610;