rs567929292

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002629.4(PGAM1):c.646A>C(p.Ile216Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000354 in 1,611,934 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000037 ( 1 hom. )

Consequence

PGAM1
NM_002629.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.19

Publications

0 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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047822).

BS2

High AC in GnomAdExome4 at 54 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.646A>C	p.Ile216Leu	missense	Exon 4 of 4	NP_002620.1	P18669
	PGAM1	NM_001317079.2		c.601A>C	p.Ile201Leu	missense	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.646A>C	p.Ile216Leu	missense	Exon 4 of 4	ENSP00000359991.4	P18669
PGAM1	ENST00000889728.1		c.634A>C	p.Ile212Leu	missense	Exon 4 of 4	ENSP00000559787.1
PGAM1	ENST00000889729.1		c.610A>C	p.Ile204Leu	missense	Exon 4 of 4	ENSP00000559788.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000676

AC:

AN:

251378

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1459796

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

726204

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33404

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000592

AC:

AN:

86166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000241

AC:

AN:

4154

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111890

Other (OTH)

AF:

0.0000332

AC:

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.0000197

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41516

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.000624

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

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:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000576

AC:

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

0.26

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.30

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.023

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.021

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.70

PhyloP100

9.2

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.0

REVEL

Uncertain

0.37

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.36

MutPred

0.55

Gain of glycosylation at T212 (P = 0.2518)

MVP

0.91

MPC

1.0

ClinPred

0.23

GERP RS

5.4

Varity_R

0.23

gMVP

0.59

Mutation Taster

=34/66

disease causing

(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