chr13-100530281-C-T

Variant names:

• chr13-100530281-C-T
• rs41281122
• NM_000282.4:c.*115C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000282.4(PCCA):​c.*115C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00935 in 850,454 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0097 (43 hom.)
• Consequence: PCCA NM_000282.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.444
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 13-100530281-C-T is Benign according to our data. Variant chr13-100530281-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 310853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00775 (1180/152294) while in subpopulation NFE AF = 0.0126 (854/68020). AF 95% confidence interval is 0.0119. There are 5 homozygotes in GnomAd4. There are 563 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.*115C>T		3_prime_UTR	Exon 24 of 24	NP_000273.2	P05165-1
	GGACT	NM_001195087.2	MANE Select	c.*1849G>A		3_prime_UTR	Exon 3 of 3	NP_001182016.1	Q9BVM4
	PCCA	NM_001352605.2		c.*115C>T		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.*115C>T		3_prime_UTR	Exon 24 of 24	ENSP00000365462.1	P05165-1
	GGACT	ENST00000683975.1	MANE Select	c.*1849G>A		3_prime_UTR	Exon 3 of 3	ENSP00000508020.1	Q9BVM4
	GGACT	ENST00000455100.2	TSL:1	c.*1849G>A		3_prime_UTR	Exon 2 of 2	ENSP00000410449.1	Q9BVM4

Frequencies

GnomAD3 genomes AF: 0.00775 AC: 1179 AN: 152176 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00205

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00739

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.00766

GnomAD4 exome AF: 0.00970 AC: 6773 AN: 698160 Hom.: 43 Cov.: 9 AF XY: 0.00943 AC XY: 3483 AN XY: 369250

African (AFR) AF: 0.00171 AC: 32 AN: 18716

American (AMR) AF: 0.00639 AC: 227 AN: 35516

Ashkenazi Jewish (ASJ) AF: 0.00990 AC: 206 AN: 20804

East Asian (EAS) AF: 0.0000296 AC: 1 AN: 33760

South Asian (SAS) AF: 0.00181 AC: 119 AN: 65678

European-Finnish (FIN) AF: 0.00546 AC: 263 AN: 48146

Middle Eastern (MID) AF: 0.00844 AC: 36 AN: 4264

European-Non Finnish (NFE) AF: 0.0128 AC: 5568 AN: 436136

Other (OTH) AF: 0.00913 AC: 321 AN: 35140

GnomAD4 genome AF: 0.00775 AC: 1180 AN: 152294 Hom.: 5 Cov.: 33 AF XY: 0.00756 AC XY: 563 AN XY: 74464

African (AFR) AF: 0.00205 AC: 85 AN: 41562

American (AMR) AF: 0.00738 AC: 113 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4826

European-Finnish (FIN) AF: 0.00471 AC: 50 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0126 AC: 854 AN: 68020

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00686 Hom.: 2

Bravo AF: 0.00784

Asia WGS AF: 0.00144 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.44
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: rs41281122; hg19: chr13-101182535;