rs7122539

Positions:

• chr11-66895260-G-A
• chr11-66895260-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.1-23101C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,796 control chromosomes in the GnomAD database, including 14,591 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 0.42 (14591 hom., cov: 30)
• Consequence: PC NM_001040716.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PC	NM_001040716.2	c.1-23101C>T		intron_variant		ENST00000393960.7	NP_001035806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PC	ENST00000393960.7	c.1-23101C>T		intron_variant		5	NM_001040716.2	ENSP00000377532	P1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63706 AN: 151678 Hom.: 14542 Cov.: 30

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.420 AC: 63805 AN: 151796 Hom.: 14591 Cov.: 30 AF XY: 0.420 AC XY: 31128 AN XY: 74186

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.466

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.398

Alfa AF: 0.351 Hom.: 20776

Bravo AF: 0.424

Asia WGS AF: 0.419 AC: 1460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.83
DANN	Benign	0.63

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: rs7122539; hg19: chr11-66662731;