rs8192381

Variant names:

• chr15-72224251-G-A
• rs8192381
• NM_002654.6:c.-13-5141C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002654.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKM	NM_002654.6	MANE Select	c.-13-5141C>T		intron	N/A	NP_002645.3
	PKM	NM_001206796.3		c.93-2967C>T		intron	N/A	NP_001193725.1
	PKM	NM_001411081.1		c.93-2967C>T		intron	N/A	NP_001398010.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKM	ENST00000335181.10	TSL:1 MANE Select	c.-13-5141C>T		intron	N/A	ENSP00000334983.5
	PKM	ENST00000565184.6	TSL:1	c.93-5141C>T		intron	N/A	ENSP00000455736.2
	PKM	ENST00000568459.5	TSL:1	c.-13-5141C>T		intron	N/A	ENSP00000456970.1

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

African (AFR) AF: 0.0542 AC: 2248 AN: 41514

American (AMR) AF: 0.0222 AC: 339 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3472

East Asian (EAS) AF: 0.161 AC: 835 AN: 5178

South Asian (SAS) AF: 0.0486 AC: 234 AN: 4818

European-Finnish (FIN) AF: 0.0404 AC: 428 AN: 10600

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0283 AC: 1922 AN: 67996

Other (OTH) AF: 0.0360 AC: 76 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.58
PhyloP100		0.0010
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: rs8192381; hg19: chr15-72516592;