rs10514

Variant names:

• chr15-72209800-G-A
• rs10514
• NM_002654.6:c.438C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-72209800-G-A
• chr15-72209800-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002654.6(PKM):​c.438C>T​(p.Asn146Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0716 in 1,613,704 control chromosomes in the GnomAD database, including 4,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (325 hom., cov: 31)
  • Exomes 𝑓: 0.073 (4253 hom.)
• Consequence: PKM NM_002654.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.607
• Publications: 12 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 15-72209800-G-A is Benign according to our data. Variant chr15-72209800-G-A is described in ClinVar as Benign. ClinVar VariationId is 403311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.607 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0762 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.438C>T	p.Asn146Asn	synonymous	Exon 5 of 11	NP_002645.3
	PKM	NM_001206796.3		c.660C>T	p.Asn220Asn	synonymous	Exon 6 of 12	NP_001193725.1	A0A804F729
	PKM	NM_001411081.1		c.660C>T	p.Asn220Asn	synonymous	Exon 6 of 12	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.438C>T	p.Asn146Asn	synonymous	Exon 5 of 11	ENSP00000334983.5	P14618-1
	PKM	ENST00000565184.6	TSL:1	c.543C>T	p.Asn181Asn	synonymous	Exon 5 of 11	ENSP00000455736.2	A0A804F6T5
	PKM	ENST00000568459.5	TSL:1	c.438C>T	p.Asn146Asn	synonymous	Exon 5 of 11	ENSP00000456970.1	P14618-2

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9178 AN: 151930 Hom.: 324 Cov.: 31

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.0842

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0855

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0780

Gnomad OTH AF: 0.0709

GnomAD2 exomes AF: 0.0610 AC: 15331 AN: 251492 AF XY: 0.0613

Gnomad AFR exome AF: 0.0290

Gnomad AMR exome AF: 0.0409

Gnomad ASJ exome AF: 0.0863

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.0866

Gnomad NFE exome AF: 0.0817

Gnomad OTH exome AF: 0.0790

GnomAD4 exome AF: 0.0727 AC: 106333 AN: 1461656 Hom.: 4253 Cov.: 32 AF XY: 0.0713 AC XY: 51872 AN XY: 727134

African (AFR) AF: 0.0329 AC: 1100 AN: 33476

American (AMR) AF: 0.0432 AC: 1930 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0828 AC: 2163 AN: 26134

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39700

South Asian (SAS) AF: 0.0301 AC: 2595 AN: 86258

European-Finnish (FIN) AF: 0.0893 AC: 4769 AN: 53418

Middle Eastern (MID) AF: 0.0827 AC: 477 AN: 5768

European-Non Finnish (NFE) AF: 0.0800 AC: 88938 AN: 1111786

Other (OTH) AF: 0.0720 AC: 4346 AN: 60392

GnomAD4 genome AF: 0.0604 AC: 9183 AN: 152048 Hom.: 325 Cov.: 31 AF XY: 0.0599 AC XY: 4450 AN XY: 74316

African (AFR) AF: 0.0327 AC: 1355 AN: 41478

American (AMR) AF: 0.0641 AC: 979 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0842 AC: 292 AN: 3466

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5168

South Asian (SAS) AF: 0.0293 AC: 141 AN: 4820

European-Finnish (FIN) AF: 0.0855 AC: 902 AN: 10544

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0780 AC: 5303 AN: 67986

Other (OTH) AF: 0.0697 AC: 147 AN: 2108

Alfa AF: 0.0734 Hom.: 179

Bravo AF: 0.0577

Asia WGS AF: 0.0270 AC: 93 AN: 3478

EpiCase AF: 0.0803

EpiControl AF: 0.0840

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.081
DANN	Benign	0.56
PhyloP100		-0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs10514; hg19: chr15-72502141; COSMIC: COSV108122349; COSMIC: COSV108122349;