15-72209800-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002654.6(PKM):​c.438C>G​(p.Asn146Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PKM NM_002654.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08582342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKM	NM_002654.6	c.438C>G	p.Asn146Lys	missense_variant	Exon 5 of 11	ENST00000335181.10	NP_002645.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKM	ENST00000335181.10	c.438C>G	p.Asn146Lys	missense_variant	Exon 5 of 11	1	NM_002654.6	ENSP00000334983.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461828 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727224

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.00034	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	0.0010
DANN	Benign	0.35
DEOGEN2	Benign	0.42	.;.;.;.;T;.;.;T;T;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.27	N
LIST_S2	Uncertain	0.88	D;D;T;.;D;.;.;D;T;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.086	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.34	.;N;.;N;N;N;N;.;.;.;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.64	N;N;.;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.91	T;T;.;T;T;T;T;T;T;T;T
Sift4G	Benign	0.79	T;T;T;T;T;T;T;T;.;.;.
Polyphen		0.0090, 0.0010	.;B;B;B;B;B;B;.;.;.;.
Vest4		0.49
MutPred		0.40		.;Gain of ubiquitination at N146 (P = 0.0276);.;Gain of ubiquitination at N146 (P = 0.0276);Gain of ubiquitination at N146 (P = 0.0276);Gain of ubiquitination at N146 (P = 0.0276);Gain of ubiquitination at N146 (P = 0.0276);Gain of ubiquitination at N146 (P = 0.0276);Gain of ubiquitination at N146 (P = 0.0276);Gain of ubiquitination at N146 (P = 0.0276);Gain of ubiquitination at N146 (P = 0.0276);
MVP		0.65
MPC		0.73
ClinPred		0.042	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-72502141;