chr13-100089129-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000282.4(PCCA):​c.9G>C​(p.Gly3Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,509,222 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: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: PCCA NM_000282.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 13-100089129-G-C is Benign according to our data. Variant chr13-100089129-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 795037.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>C	p.Gly3Gly	synonymous	Exon 1 of 24	NP_000273.2	P05165-1
	PCCA	NM_001352605.2		c.9G>C	p.Gly3Gly	synonymous	Exon 1 of 23	NP_001339534.1
	PCCA	NM_001127692.3		c.9G>C	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>C	p.Gly3Gly	synonymous	Exon 1 of 24	ENSP00000365462.1	P05165-1
	PCCA	ENST00000881637.1		c.9G>C	p.Gly3Gly	synonymous	Exon 1 of 25	ENSP00000551696.1
	PCCA	ENST00000881640.1		c.9G>C	p.Gly3Gly	synonymous	Exon 1 of 25	ENSP00000551699.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000219 AC: 3 AN: 137272 AF XY: 0.0000269

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000103 AC: 14 AN: 1356872 Hom.: 0 Cov.: 31 AF XY: 0.0000120 AC XY: 8 AN XY: 666244

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: 0.000178 AC: 13 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: 0.00 AC: 0 AN: 1058836

Other (OTH) AF: 0.0000178 AC: 1 AN: 56068

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152350 Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2 AN XY: 74500

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15312

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	2	Propionic acidemia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.62
PhyloP100		-0.86
PromoterAI		0.26	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;