NM_002633.3:c.399T>A

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_002633.3(PGM1):​c.399T>A​(p.Ile133Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. I133I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGM1 NM_002633.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 1-63629577-T-A is Benign according to our data. Variant chr1-63629577-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2699106.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.006 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGM1	NM_002633.3	c.399T>A	p.Ile133Ile	synonymous_variant	Exon 2 of 11	ENST00000371084.8	NP_002624.2
PGM1	NM_001172818.1	c.453T>A	p.Ile151Ile	synonymous_variant	Exon 2 of 11		NP_001166289.1
PGM1	NM_001172819.2	c.-193T>A		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>A	p.Ile133Ile	synonymous_variant	Exon 2 of 11	1	NM_002633.3	ENSP00000360125.3
PGM1	ENST00000650546.1	c.399T>A	p.Ile133Ile	synonymous_variant	Exon 2 of 12			ENSP00000497812.1
PGM1	ENST00000371083.4	c.453T>A	p.Ile151Ile	synonymous_variant	Exon 2 of 11	2		ENSP00000360124.4
PGM1	ENST00000540265	c.-193T>A		5_prime_UTR_variant	Exon 2 of 11	2		ENSP00000443449.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

PGM1-congenital disorder of glycosylation Benign:1

Dec 07, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.3
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;