rs140035988

Variant names:

• chr1-63638799-C-G
• rs140035988
• NM_002633.3:c.1143C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-63638799-C-G
• chr1-63638799-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_002633.3(PGM1):​c.1143C>G​(p.Thr381Thr) variant causes a splice region, 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T381T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGM1 NM_002633.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.00004684
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• 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: Genomics England PanelApp, Ambry Genetics, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-1.16 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM1	NM_002633.3	MANE Select	c.1143C>G	p.Thr381Thr	splice_region synonymous	Exon 7 of 11	NP_002624.2
	PGM1	NM_001172818.1		c.1197C>G	p.Thr399Thr	splice_region synonymous	Exon 7 of 11	NP_001166289.1
	PGM1	NM_001172819.2		c.552C>G	p.Thr184Thr	splice_region synonymous	Exon 7 of 11	NP_001166290.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM1	ENST00000371084.8	TSL:1 MANE Select	c.1143C>G	p.Thr381Thr	splice_region synonymous	Exon 7 of 11	ENSP00000360125.3
	PGM1	ENST00000650546.1		c.1143C>G	p.Thr381Thr	splice_region synonymous	Exon 7 of 12	ENSP00000497812.1
	PGM1	ENST00000371083.4	TSL:2	c.1197C>G	p.Thr399Thr	splice_region synonymous	Exon 7 of 11	ENSP00000360124.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.075
DANN	Benign	0.60
PhyloP100		-1.2
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000047
dbscSNV1_RF	Benign	0.010
SpliceAI score (max)		0.14		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: rs140035988; hg19: chr1-64104470;