rs147037340

Variant names:

• chr13-100111929-ATTAT-A
• rs147037340
• NM_000282.4:c.231+47_231+50delTATT

Your query was ambiguous. Multiple possible variants found:

• chr13-100111929-ATTAT-A
• chr13-100111929-ATTAT-ATTATTTAT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000282.4(PCCA):​c.231+47_231+50delTATT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0951 in 1,586,396 control chromosomes in the GnomAD database, including 7,910 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (687 hom., cov: 30)
  • Exomes 𝑓: 0.095 (7223 hom.)
• Consequence: PCCA NM_000282.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.24
• 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 Gene-Disease associations (from GenCC):

• propionic acidemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, G2P

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 13-100111929-ATTAT-A is Benign according to our data. Variant chr13-100111929-ATTAT-A is described in ClinVar as Benign. ClinVar VariationId is 255735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

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.231+47_231+50delTATT		intron	N/A	NP_000273.2	P05165-1
	PCCA	NM_001352605.2		c.231+47_231+50delTATT		intron	N/A	NP_001339534.1
	PCCA	NM_001127692.3		c.153+47_153+50delTATT		intron	N/A	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.231+42_231+45delTTAT		intron	N/A	ENSP00000365462.1	P05165-1
	PCCA	ENST00000881637.1		c.231+42_231+45delTTAT		intron	N/A	ENSP00000551696.1
	PCCA	ENST00000881640.1		c.231+42_231+45delTTAT		intron	N/A	ENSP00000551699.1

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14123 AN: 152030 Hom.: 684 Cov.: 30

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0868

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0588

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.0856 AC: 21325 AN: 249048 AF XY: 0.0891

Gnomad AFR exome AF: 0.0963

Gnomad AMR exome AF: 0.0602

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.000437

Gnomad FIN exome AF: 0.0570

Gnomad NFE exome AF: 0.0992

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0953 AC: 136698 AN: 1434248 Hom.: 7223 AF XY: 0.0958 AC XY: 68548 AN XY: 715184

African (AFR) AF: 0.0980 AC: 3225 AN: 32914

American (AMR) AF: 0.0635 AC: 2835 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 3205 AN: 25942

East Asian (EAS) AF: 0.000558 AC: 22 AN: 39424

South Asian (SAS) AF: 0.112 AC: 9617 AN: 85606

European-Finnish (FIN) AF: 0.0581 AC: 3099 AN: 53354

Middle Eastern (MID) AF: 0.142 AC: 753 AN: 5294

European-Non Finnish (NFE) AF: 0.0994 AC: 108137 AN: 1087714

Other (OTH) AF: 0.0978 AC: 5805 AN: 59372

GnomAD4 genome AF: 0.0929 AC: 14134 AN: 152148 Hom.: 687 Cov.: 30 AF XY: 0.0913 AC XY: 6796 AN XY: 74408

African (AFR) AF: 0.101 AC: 4206 AN: 41494

American (AMR) AF: 0.0868 AC: 1327 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 387 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5182

South Asian (SAS) AF: 0.105 AC: 504 AN: 4820

European-Finnish (FIN) AF: 0.0588 AC: 623 AN: 10594

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.0994 AC: 6757 AN: 67982

Other (OTH) AF: 0.101 AC: 214 AN: 2114

Alfa AF: 0.0962 Hom.: 67

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Propionic acidemia (4)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs147037340; hg19: chr13-100764183;