rs8192431

Positions:

• chr15-72200011-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.1490-255C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,996 control chromosomes in the GnomAD database, including 3,251 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 0.20 (3251 hom., cov: 32)
• Consequence: PKM NM_002654.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKM	NM_002654.6	c.1490-255C>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.1490-255C>T		intron_variant		1	NM_002654.6	ENSP00000334983	P4

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30311 AN: 151878 Hom.: 3254 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.199 AC: 30322 AN: 151996 Hom.: 3251 Cov.: 32 AF XY: 0.201 AC XY: 14922 AN XY: 74280

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.209

Alfa AF: 0.204 Hom.: 1716

Bravo AF: 0.201

Asia WGS AF: 0.363 AC: 1259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.84

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: rs8192431; hg19: chr15-72492352;