15-72208731-C-T

Variant names:

• chr15-72208731-C-T
• rs11558376
• NM_002654.6:c.726G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002654.6(PKM):​c.726G>A​(p.Ala242Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,614,130 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (13 hom.)
• Consequence: PKM NM_002654.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.47
• 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]

ENSG00000303314 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 15-72208731-C-T is Benign according to our data. Variant chr15-72208731-C-T is described in ClinVar as Benign. ClinVar VariationId is 730512.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.47 with no splicing effect.
• BS2: High AC in GnomAd4 at 305 AD gene.

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.726G>A	p.Ala242Ala	synonymous	Exon 6 of 11	NP_002645.3
	PKM	NM_001206796.3		c.948G>A	p.Ala316Ala	synonymous	Exon 7 of 12	NP_001193725.1	A0A804F729
	PKM	NM_001411081.1		c.948G>A	p.Ala316Ala	synonymous	Exon 7 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.726G>A	p.Ala242Ala	synonymous	Exon 6 of 11	ENSP00000334983.5	P14618-1
	PKM	ENST00000565184.6	TSL:1	c.831G>A	p.Ala277Ala	synonymous	Exon 6 of 11	ENSP00000455736.2	A0A804F6T5
	PKM	ENST00000568459.5	TSL:1	c.726G>A	p.Ala242Ala	synonymous	Exon 6 of 11	ENSP00000456970.1	P14618-2

Frequencies

GnomAD3 genomes AF: 0.00200 AC: 305 AN: 152128 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.00215 AC: 541 AN: 251488 AF XY: 0.00210

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0181

Gnomad NFE exome AF: 0.00121

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.00149 AC: 2183 AN: 1461884 Hom.: 13 Cov.: 32 AF XY: 0.00145 AC XY: 1058 AN XY: 727246

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.0164 AC: 876 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00112 AC: 1244 AN: 1112006

Other (OTH) AF: 0.000811 AC: 49 AN: 60394

GnomAD4 genome AF: 0.00200 AC: 305 AN: 152246 Hom.: 4 Cov.: 31 AF XY: 0.00294 AC XY: 219 AN XY: 74444

African (AFR) AF: 0.000217 AC: 9 AN: 41546

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0197 AC: 209 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00122 AC: 83 AN: 68014

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00116 Hom.: 0

Bravo AF: 0.000589

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000981

EpiControl AF: 0.000830

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.46
DANN	Benign	0.76
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11558376; hg19: chr15-72501072;