Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_015599.3(PGM3):c.248T>C(p.Leu83Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. L83L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

PGM3
NM_015599.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:2

Conservation

PhyloP100: 8.91

Publications

8 publications found

Variant links:

Genes affected

PGM3 (HGNC:8907): (phosphoglucomutase 3) This gene encodes a member of the phosphohexose mutase family. The encoded protein mediates both glycogen formation and utilization by catalyzing the interconversion of glucose-1-phosphate and glucose-6-phosphate. A non-synonymous single nucleotide polymorphism in this gene may play a role in resistance to diabetic nephropathy and neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

PGM3 Gene-Disease associations (from GenCC):

immunodeficiency 23
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

PGM3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.945

PP5

Variant 6-83188755-A-G is Pathogenic according to our data. Variant chr6-83188755-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 133320.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015599.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PGM3	NM_015599.3	MANE Select	c.248T>C	p.Leu83Ser	missense	Exon 3 of 13	NP_056414.1
PGM3	NM_001199917.2		c.332T>C	p.Leu111Ser	missense	Exon 4 of 14	NP_001186846.1
PGM3	NM_001367287.1		c.332T>C	p.Leu111Ser	missense	Exon 4 of 14	NP_001354216.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PGM3	ENST00000513973.6	TSL:1 MANE Select	c.248T>C	p.Leu83Ser	missense	Exon 3 of 13	ENSP00000424874.1
PGM3	ENST00000512866.5	TSL:1	c.248T>C	p.Leu83Ser	missense	Exon 3 of 14	ENSP00000421565.1
PGM3	ENST00000283977.9	TSL:5	c.5T>C	p.Leu2Ser	missense	Exon 2 of 12	ENSP00000283977.5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hyper-IgE syndrome (1)

Immunodeficiency 23 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.97

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.95

MetaSVM

Uncertain

0.48

MutationAssessor

Pathogenic

3.5

PhyloP100

8.9

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-5.8

REVEL

Pathogenic

0.88

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.86

MutPred

0.79

Gain of disorder (P = 0.0081)

MVP

0.96

MPC

0.91

ClinPred

1.0

GERP RS

5.8

PromoterAI

0.0052

Neutral

(source)

Varity_R

0.78

gMVP

0.91

Mutation Taster

=2/98

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_015599.3:c.248T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over