11-66932151-G-C

Position:

• chr11-66932151-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040716.2(PC):​c.-1+20279C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,066 control chromosomes in the GnomAD database, including 6,868 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6868 hom., cov: 31)
• Consequence: PC NM_001040716.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

Genes affected

PC (HGNC:8636): (pyruvate carboxylase) This gene encodes pyruvate carboxylase, which requires biotin and ATP to catalyse the carboxylation of pyruvate to oxaloacetate. The active enzyme is a homotetramer arranged in a tetrahedron which is located exclusively in the mitochondrial matrix. Pyruvate carboxylase is involved in gluconeogenesis, lipogenesis, insulin secretion and synthesis of the neurotransmitter glutamate. Mutations in this gene have been associated with pyruvate carboxylase deficiency. Alternatively spliced transcript variants with different 5' UTRs, but encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PC	NM_001040716.2	c.-1+20279C>G		intron_variant		ENST00000393960.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PC	ENST00000393960.7	c.-1+20279C>G		intron_variant		5	NM_001040716.2	P1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44782 AN: 151948 Hom.: 6859 Cov.: 31

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.295

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.295 AC: 44820 AN: 152066 Hom.: 6868 Cov.: 31 AF XY: 0.292 AC XY: 21684 AN XY: 74334

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.296

Alfa AF: 0.206 Hom.: 489

Bravo AF: 0.288

Asia WGS AF: 0.226 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.64

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: rs7108388; hg19: chr11-66699622;