rs111778723

Variant names:

• chr13-100111820-ATG-A
• rs111778723
• NM_000282.4:c.184-17_184-16delGT

Your query was ambiguous. Multiple possible variants found:

• chr13-100111820-ATG-A
• chr13-100111820-ATG-ATGTG

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.184-17_184-16delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,563,578 control chromosomes in the GnomAD database, including 9,092 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1214 hom., cov: 30)
  • Exomes 𝑓: 0.10 (7878 hom.)
• Consequence: PCCA NM_000282.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.885
• Publications: 2 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 13-100111820-ATG-A is Benign according to our data. Variant chr13-100111820-ATG-A is described in ClinVar as Benign. ClinVar VariationId is 196244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 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.184-17_184-16delGT		intron	N/A	NP_000273.2	P05165-1
	PCCA	NM_001352605.2		c.184-17_184-16delGT		intron	N/A	NP_001339534.1
	PCCA	NM_001127692.3		c.106-17_106-16delGT		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.184-20_184-19delTG		intron	N/A	ENSP00000365462.1	P05165-1
	PCCA	ENST00000881637.1		c.184-20_184-19delTG		intron	N/A	ENSP00000551696.1
	PCCA	ENST00000881640.1		c.184-20_184-19delTG		intron	N/A	ENSP00000551699.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17897 AN: 151908 Hom.: 1212 Cov.: 30

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0589

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.132

GnomAD2 exomes AF: 0.0929 AC: 22682 AN: 244140 AF XY: 0.0949

Gnomad AFR exome AF: 0.173

Gnomad AMR exome AF: 0.0699

Gnomad ASJ exome AF: 0.139

Gnomad EAS exome AF: 0.000443

Gnomad FIN exome AF: 0.0564

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.0995 AC: 140483 AN: 1411550 Hom.: 7878 AF XY: 0.0997 AC XY: 70282 AN XY: 704592

African (AFR) AF: 0.183 AC: 5937 AN: 32394

American (AMR) AF: 0.0734 AC: 3244 AN: 44216

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3618 AN: 25756

East Asian (EAS) AF: 0.000534 AC: 21 AN: 39322

South Asian (SAS) AF: 0.113 AC: 9519 AN: 84566

European-Finnish (FIN) AF: 0.0579 AC: 3079 AN: 53170

Middle Eastern (MID) AF: 0.159 AC: 738 AN: 4646

European-Non Finnish (NFE) AF: 0.101 AC: 107988 AN: 1068930

Other (OTH) AF: 0.108 AC: 6339 AN: 58550

GnomAD4 genome AF: 0.118 AC: 17933 AN: 152028 Hom.: 1214 Cov.: 30 AF XY: 0.115 AC XY: 8560 AN XY: 74326

African (AFR) AF: 0.180 AC: 7446 AN: 41434

American (AMR) AF: 0.104 AC: 1593 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3464

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5174

South Asian (SAS) AF: 0.105 AC: 505 AN: 4820

European-Finnish (FIN) AF: 0.0589 AC: 622 AN: 10564

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6916 AN: 67970

Other (OTH) AF: 0.131 AC: 275 AN: 2106

Alfa AF: 0.114 Hom.: 194

Bravo AF: 0.123

Asia WGS AF: 0.0570 AC: 196 AN: 3464

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	4	Propionic acidemia (4)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89
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: rs111778723; hg19: chr13-100764074; COSMIC: COSV66189957;