Variant rs10514 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002654.6(PKM):c.438C>T(p.Asn146=) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.607

Variant links:

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]

PKM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKM	NM_002654.6 linkuse as main transcript	c.438C>T	p.Asn146=	synonymous_variant	5/11	ENST00000335181.10	NP_002645.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKM	ENST00000335181.10 linkuse as main transcript	c.438C>T	p.Asn146=	synonymous_variant	5/11	1	NM_002654.6	ENSP00000334983	P4	P14618-1

Frequencies

GnomAD3 genomes

AF:

0.0604

AC:

9178

AN:

151930

Hom.:

324

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0610

AC:

15331

AN:

251492

Hom.:

569

AF XY:

0.0613

AC XY:

8334

AN XY:

135920

show subpopulations

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 SAS exome

AF:

0.0296

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.:

AF XY:

0.0713

AC XY:

51872

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.0329

Gnomad4 AMR exome

AF:

0.0432

Gnomad4 ASJ exome

AF:

0.0828

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0301

Gnomad4 FIN exome

AF:

0.0893

Gnomad4 NFE exome

AF:

0.0800

Gnomad4 OTH exome

AF:

0.0720

GnomAD4 genome

AF:

0.0604

AC:

9183

AN:

152048

Hom.:

325

Cov.:

AF XY:

0.0599

AC XY:

4450

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0327

Gnomad4 AMR

AF:

0.0641

Gnomad4 ASJ

AF:

0.0842

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.0293

Gnomad4 FIN

AF:

0.0855

Gnomad4 NFE

AF:

0.0780

Gnomad4 OTH

AF:

0.0697

Alfa

AF:

0.0738

Hom.:

178

Bravo

AF:

0.0577

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0803

EpiControl

AF:

0.0840

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.081

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over