rs756333282

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002629.4(PGAM1):c.598C>G(p.Leu200Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000565 in 1,611,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L200F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

PGAM1
NM_002629.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.44

Publications

2 publications found

Variant links:

Genes affected

PGAM1 (HGNC:8888): (phosphoglycerate mutase 1) The protein encoded by this gene is a mutase that catalyzes the reversible reaction of 3-phosphoglycerate (3-PGA) to 2-phosphoglycerate (2-PGA) in the glycolytic pathway. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

PGAM1 links:

EXOSC1 (HGNC:17286): (exosome component 1) This gene encodes a core component of the exosome. The mammalian exosome is required for rapid degradation of AU rich element-containing RNAs but not for poly(A) shortening. The association of this protein with the exosome is mediated by protein-protein interactions with ribosomal RNA-processing protein 42 and ribosomal RNA-processing protein 46. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2016]

EXOSC1 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia, type 1F
Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

EXOSC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17992896).

BS2

High AC in GnomAd4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002629.4. 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
	PGAM1	NM_002629.4	MANE Select	c.598C>G	p.Leu200Val	missense splice_region	Exon 4 of 4	NP_002620.1	P18669
	PGAM1	NM_001317079.2		c.553C>G	p.Leu185Val	missense splice_region	Exon 4 of 4	NP_001304008.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PGAM1	ENST00000334828.6	TSL:1 MANE Select	c.598C>G	p.Leu200Val	missense splice_region	Exon 4 of 4	ENSP00000359991.4	P18669
PGAM1	ENST00000889729.1		c.562C>G	p.Leu188Val	missense splice_region	Exon 4 of 4	ENSP00000559788.1
PGAM1	ENST00000940113.1		c.541C>G	p.Leu181Val	missense splice_region	Exon 4 of 4	ENSP00000610172.1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000517

AC:

AN:

251390

AF XY:

0.0000515

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000534

AC:

AN:

1459806

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

726202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.000262

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4150

European-Non Finnish (NFE)

AF:

0.0000549

AC:

AN:

1111906

Other (OTH)

AF:

0.0000498

AC:

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68028

Other (OTH)

AF:

0.000478

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000503

Hom.:

Bravo

AF:

0.0000604

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.18

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

Eigen

Benign

0.023

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.77

M_CAP

Benign

0.018

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.8

PhyloP100

5.4

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.22

REVEL

Benign

0.26

Sift

Benign

0.15

Sift4G

Benign

0.17

Polyphen

0.0010

Vest4

0.23

MVP

0.61

MPC

1.1

ClinPred

0.13

GERP RS

5.5

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.47

gMVP

0.54

Mutation Taster

=69/31

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over