15-72204421-T-C

Variant names:

• chr15-72204421-T-C
• rs2856929
• NM_002654.6:c.1141-1801A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002654.6(PKM):​c.1141-1801A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,146 control chromosomes in the GnomAD database, including 3,887 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 0.22 (3887 hom., cov: 32)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: PKM NM_002654.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925
• Publications: 10 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]

ENSG00000303314 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKM	NM_002654.6	MANE Select	c.1141-1801A>G		intron	N/A	NP_002645.3
	PKM	NM_001206796.3		c.1363-1233A>G		intron	N/A	NP_001193725.1	A0A804F729
	PKM	NM_001411081.1		c.1363-1801A>G		intron	N/A	NP_001398010.1	A0A8V8TNX9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKM	ENST00000335181.10	TSL:1 MANE Select	c.1141-1801A>G		intron	N/A	ENSP00000334983.5	P14618-1
	PKM	ENST00000565184.6	TSL:1	c.1246-1233A>G		intron	N/A	ENSP00000455736.2	A0A804F6T5
	PKM	ENST00000568459.5	TSL:1	c.1141-1233A>G		intron	N/A	ENSP00000456970.1	P14618-2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33267 AN: 152008 Hom.: 3885 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.200 AC: 4 AN: 20 Hom.: 0 Cov.: 0 AF XY: 0.188 AC XY: 3 AN XY: 16

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 4 AN: 20

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.219 AC: 33304 AN: 152126 Hom.: 3887 Cov.: 32 AF XY: 0.221 AC XY: 16440 AN XY: 74354

African (AFR) AF: 0.184 AC: 7648 AN: 41492

American (AMR) AF: 0.280 AC: 4285 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 735 AN: 3470

East Asian (EAS) AF: 0.416 AC: 2150 AN: 5168

South Asian (SAS) AF: 0.252 AC: 1213 AN: 4814

European-Finnish (FIN) AF: 0.210 AC: 2224 AN: 10584

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14378 AN: 67988

Other (OTH) AF: 0.231 AC: 488 AN: 2112

Alfa AF: 0.216 Hom.: 4468

Bravo AF: 0.226

Asia WGS AF: 0.383 AC: 1328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.10
DANN	Benign	0.62
PhyloP100		-0.93
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: rs2856929; hg19: chr15-72496762;