13-100089144-A-G

Variant names:

• chr13-100089144-A-G
• rs117397004
• NM_000282.4:c.24A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000282.4(PCCA):​c.24A>G​(p.Thr8Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000612 in 1,522,960 control chromosomes in the GnomAD database, including 17 homozygotes. 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. T8T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00063 (17 hom.)
• Consequence: PCCA NM_000282.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.23
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 13-100089144-A-G is Benign according to our data. Variant chr13-100089144-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.23 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000407 (62/152324) while in subpopulation EAS AF = 0.0112 (58/5178). AF 95% confidence interval is 0.0089. There are 0 homozygotes in GnomAd4. There are 33 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 17 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.24A>G	p.Thr8Thr	synonymous	Exon 1 of 24	NP_000273.2	P05165-1
	PCCA	NM_001352605.2		c.24A>G	p.Thr8Thr	synonymous	Exon 1 of 23	NP_001339534.1
	PCCA	NM_001127692.3		c.24A>G	p.Thr8Thr	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.24A>G	p.Thr8Thr	synonymous	Exon 1 of 24	ENSP00000365462.1	P05165-1
	PCCA	ENST00000881637.1		c.24A>G	p.Thr8Thr	synonymous	Exon 1 of 25	ENSP00000551696.1
	PCCA	ENST00000881640.1		c.24A>G	p.Thr8Thr	synonymous	Exon 1 of 25	ENSP00000551699.1

Frequencies

GnomAD3 genomes AF: 0.000407 AC: 62 AN: 152208 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: 0.0112

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000391 AC: 54 AN: 138140 AF XY: 0.000373

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000441

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00516

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000635 AC: 870 AN: 1370636 Hom.: 17 Cov.: 31 AF XY: 0.000673 AC XY: 454 AN XY: 674786

African (AFR) AF: 0.0000687 AC: 2 AN: 29104

American (AMR) AF: 0.0000289 AC: 1 AN: 34624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24034

East Asian (EAS) AF: 0.0248 AC: 831 AN: 33510

South Asian (SAS) AF: 0.000147 AC: 11 AN: 74712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4666

European-Non Finnish (NFE) AF: 0.0000112 AC: 12 AN: 1067798

Other (OTH) AF: 0.000229 AC: 13 AN: 56832

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152324 Hom.: 0 Cov.: 33 AF XY: 0.000443 AC XY: 33 AN XY: 74480

African (AFR) AF: 0.00 AC: 0 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5178

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000856 Hom.: 0

Bravo AF: 0.000219

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Propionic acidemia (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.21
DANN	Benign	0.40
PhyloP100		-2.2
PromoterAI		0.14	Neutral
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: rs117397004; hg19: chr13-100741398;