rs547209141

Variant names:

• chr13-100089129-G-A
• rs547209141
• NM_000282.4:c.9G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-100089129-G-A
• chr13-100089129-G-C
• chr13-100089129-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000282.4(PCCA):​c.9G>A​(p.Gly3Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,356,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G3G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: PCCA NM_000282.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.856
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 13-100089129-G-A is Benign according to our data. Variant chr13-100089129-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2732732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.856 with no splicing effect.

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.9G>A	p.Gly3Gly	synonymous	Exon 1 of 24	NP_000273.2	P05165-1
	PCCA	NM_001352605.2		c.9G>A	p.Gly3Gly	synonymous	Exon 1 of 23	NP_001339534.1
	PCCA	NM_001127692.3		c.9G>A	p.Gly3Gly	synonymous	Exon 1 of 23	NP_001121164.1	P05165-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCCA	ENST00000376285.6	TSL:1 MANE Select	c.9G>A	p.Gly3Gly	synonymous	Exon 1 of 24	ENSP00000365462.1	P05165-1
	PCCA	ENST00000881637.1		c.9G>A	p.Gly3Gly	synonymous	Exon 1 of 25	ENSP00000551696.1
	PCCA	ENST00000881640.1		c.9G>A	p.Gly3Gly	synonymous	Exon 1 of 25	ENSP00000551699.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1356872 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 666244

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28664

American (AMR) AF: 0.00 AC: 0 AN: 33082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23728

East Asian (EAS) AF: 0.00 AC: 0 AN: 32796

South Asian (SAS) AF: 0.00 AC: 0 AN: 73168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4856

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1058836

Other (OTH) AF: 0.00 AC: 0 AN: 56068

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

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	-0.81
CADD	Benign	5.3
DANN	Benign	0.78
PhyloP100		-0.86
PromoterAI		-0.067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs547209141; hg19: chr13-100741383;