chr13-100089135-G-T

Variant names:

• chr13-100089135-G-T
• rs11539554
• NM_000282.4:c.15G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000282.4(PCCA):​c.15G>T​(p.Trp5Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCCA NM_000282.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCCA	NM_000282.4	c.15G>T	p.Trp5Cys	missense_variant	Exon 1 of 24	ENST00000376285.6	NP_000273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCCA	ENST00000376285.6	c.15G>T	p.Trp5Cys	missense_variant	Exon 1 of 24	1	NM_000282.4	ENSP00000365462.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1359574 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 668212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	21
DANN	Benign	0.61
DEOGEN2	Uncertain	0.44	.;.;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.76	T;T;T
M_CAP	Pathogenic	0.65	D
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Benign	0.90	L;L;L
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.14	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.42
MutPred		0.51		Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);Loss of MoRF binding (P = 0.0051);
MVP		0.91
MPC		0.23
ClinPred		0.48	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs11539554; hg19: chr13-100741389;