chr13-100089107-C-T

Variant names:

• chr13-100089107-C-T
• rs113438150
• NM_000282.4:c.-14C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000282.4(PCCA):​c.-14C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000396 in 1,481,524 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: PCCA NM_000282.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05
• 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]

PCCA-DT (HGNC:53266): (PCCA divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 13-100089107-C-T is Benign according to our data. Variant chr13-100089107-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 387987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00212 (323/152360) while in subpopulation AFR AF = 0.00748 (311/41596). AF 95% confidence interval is 0.00679. There are 3 homozygotes in GnomAd4. There are 144 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 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.-14C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 24	NP_000273.2	P05165-1
	PCCA	NM_000282.4	MANE Select	c.-14C>T		5_prime_UTR	Exon 1 of 24	NP_000273.2	P05165-1
	PCCA	NM_001352605.2		c.-14C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 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.-14C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 24	ENSP00000365462.1	P05165-1
	PCCA	ENST00000376285.6	TSL:1 MANE Select	c.-14C>T		5_prime_UTR	Exon 1 of 24	ENSP00000365462.1	P05165-1
	PCCA	ENST00000881637.1		c.-14C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 25	ENSP00000551696.1

Frequencies

GnomAD3 genomes AF: 0.00211 AC: 321 AN: 152242 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00745

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000298 AC: 36 AN: 120814 AF XY: 0.000199

Gnomad AFR exome AF: 0.00636

Gnomad AMR exome AF: 0.000321

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000199 AC: 264 AN: 1329164 Hom.: 1 Cov.: 30 AF XY: 0.000185 AC XY: 120 AN XY: 649898

African (AFR) AF: 0.00799 AC: 221 AN: 27668

American (AMR) AF: 0.000302 AC: 9 AN: 29778

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23032

East Asian (EAS) AF: 0.00 AC: 0 AN: 31090

South Asian (SAS) AF: 0.0000289 AC: 2 AN: 69316

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5044

European-Non Finnish (NFE) AF: 0.00000192 AC: 2 AN: 1043032

Other (OTH) AF: 0.000547 AC: 30 AN: 54846

GnomAD4 genome AF: 0.00212 AC: 323 AN: 152360 Hom.: 3 Cov.: 33 AF XY: 0.00193 AC XY: 144 AN XY: 74496

African (AFR) AF: 0.00748 AC: 311 AN: 41596

American (AMR) AF: 0.000392 AC: 6 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00120 Hom.: 0

Bravo AF: 0.00232

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.1
DANN	Benign	0.75
PhyloP100		-1.1
PromoterAI		-0.094	Neutral
Mutation Taster		=300/0	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: rs113438150; hg19: chr13-100741361;