chr1-63629577-T-G

Variant names:

• chr1-63629577-T-G
• rs1126727
• NM_002633.3:c.399T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001172819.2(PGM1):​c.-193T>G variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PGM1 NM_001172819.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 0 publications found

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]

PGM1 Gene-Disease associations (from GenCC):

• PGM1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Genomics England PanelApp, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22438735).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172819.2. 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
	PGM1	NM_002633.3	MANE Select	c.399T>G	p.Ile133Met	missense	Exon 2 of 11	NP_002624.2
	PGM1	NM_001172819.2		c.-193T>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	NP_001166290.1	P36871-3
	PGM1	NM_001172818.1		c.453T>G	p.Ile151Met	missense	Exon 2 of 11	NP_001166289.1	P36871-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM1	ENST00000371084.8	TSL:1 MANE Select	c.399T>G	p.Ile133Met	missense	Exon 2 of 11	ENSP00000360125.3	P36871-1
	PGM1	ENST00000540265.5	TSL:2	c.-193T>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	ENSP00000443449.1	P36871-3
	PGM1	ENST00000895883.1		c.399T>G	p.Ile133Met	missense	Exon 2 of 12	ENSP00000565942.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111734

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.0060
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.22
Sift	Benign	0.42	T
Sift4G	Benign	0.39	T
Polyphen		0.56	P
Vest4		0.51
MutPred		0.38		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
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs1126727; hg19: chr1-64095248;