NM_002633.3:c.399T>G

Variant names:

• chr1-63629577-T-G
• NM_002633.3:c.399T>G

Variant summary

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

The NM_002633.3(PGM1):​c.399T>G​(p.Ile133Met) 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 1,461,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I133I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PGM1 NM_002633.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

Genes affected

PGM1 (HGNC:8905): (phosphoglucomutase 1) The protein encoded by this gene is an isozyme of phosphoglucomutase (PGM) and belongs to the phosphohexose mutase family. There are several PGM isozymes, which are encoded by different genes and catalyze the transfer of phosphate between the 1 and 6 positions of glucose. In most cell types, this PGM isozyme is predominant, representing about 90% of total PGM activity. In red cells, PGM2 is a major isozyme. This gene is highly polymorphic. Mutations in this gene cause glycogen storage disease type 14. Alternativley spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Mar 2010]

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=0.22438735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGM1	NM_002633.3	c.399T>G	p.Ile133Met	missense_variant	Exon 2 of 11	ENST00000371084.8	NP_002624.2
PGM1	NM_001172819.2	c.-193T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 11		NP_001166290.1
PGM1	NM_001172818.1	c.453T>G	p.Ile151Met	missense_variant	Exon 2 of 11		NP_001166289.1
PGM1	NM_001172819.2	c.-193T>G		5_prime_UTR_variant	Exon 2 of 11		NP_001166290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGM1	ENST00000371084.8	c.399T>G	p.Ile133Met	missense_variant	Exon 2 of 11	1	NM_002633.3	ENSP00000360125.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461504 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727046

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: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.48	T;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.5	L;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.91	N;.;N
REVEL	Benign	0.22
Sift	Benign	0.42	T;.;T
Sift4G	Benign	0.39	T;.;T
Polyphen		0.56	P;.;B
Vest4		0.51
MutPred		0.38		Gain of disorder (P = 0.069);Gain of disorder (P = 0.069);.;
MVP		0.70
MPC		0.34
ClinPred		0.27	T
GERP RS		2.9
Varity_R		0.33
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-64095248;