rs8192381

Positions:

• chr15-72224251-G-A

Variant summary

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

The NM_002654.6(PKM):​c.-13-5141C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 152,180 control chromosomes in the GnomAD database, including 211 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 0.040 (211 hom., cov: 31)
• Consequence: PKM NM_002654.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

Genes affected

PKM (HGNC:9021): (pyruvate kinase M1/2) This gene encodes a protein involved in glycolysis. The encoded protein is a pyruvate kinase that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate to ADP, generating ATP and pyruvate. This protein has been shown to interact with thyroid hormone and may mediate cellular metabolic effects induced by thyroid hormones. This protein has been found to bind Opa protein, a bacterial outer membrane protein involved in gonococcal adherence to and invasion of human cells, suggesting a role of this protein in bacterial pathogenesis. Several alternatively spliced transcript variants encoding a few distinct isoforms have been reported. [provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKM	NM_002654.6	c.-13-5141C>T		intron_variant		ENST00000335181.10	NP_002645.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKM	ENST00000335181.10	c.-13-5141C>T		intron_variant		1	NM_002654.6	ENSP00000334983	P4

Frequencies

GnomAD3 genomes AF: 0.0404 AC: 6150 AN: 152062 Hom.: 213 Cov.: 31

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.0404

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0283

Gnomad OTH AF: 0.0364

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

GnomAD4 genome AF: 0.0404 AC: 6155 AN: 152180 Hom.: 211 Cov.: 31 AF XY: 0.0414 AC XY: 3081 AN XY: 74392

Gnomad4 AFR AF: 0.0542

Gnomad4 AMR AF: 0.0222

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.0486

Gnomad4 FIN AF: 0.0404

Gnomad4 NFE AF: 0.0283

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0376 Hom.: 27

Bravo AF: 0.0390

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.58

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: rs8192381; hg19: chr15-72516592;