chr6-83178680-ACTT-A

Variant names:

• chr6-83178680-ACTT-A
• rs267608259
• NM_015599.3:c.1019_1021delAAG

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_015599.3(PGM3):​c.1019_1021delAAG​(p.Glu340del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000000698 in 1,432,524 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PGM3 NM_015599.3 disruptive_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_015599.3. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 6-83178680-ACTT-A is Pathogenic according to our data. Variant chr6-83178680-ACTT-A is described in ClinVar as [Pathogenic]. Clinvar id is 156471.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGM3	NM_015599.3	c.1019_1021delAAG	p.Glu340del	disruptive_inframe_deletion	Exon 8 of 13	ENST00000513973.6	NP_056414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PGM3	ENST00000513973.6	c.1019_1021delAAG	p.Glu340del	disruptive_inframe_deletion	Exon 8 of 13	1	NM_015599.3	ENSP00000424874.1
PGM3	ENST00000283977.9	c.776_778delAAG	p.Glu259del	disruptive_inframe_deletion	Exon 7 of 12	5		ENSP00000283977.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432524 Hom.: 0 AF XY: 0.00000140 AC XY: 1 AN XY: 714730

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: 0.00

Gnomad4 NFE exome AF: 9.21e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hyper-IgE syndrome Pathogenic:1

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Centre of Chronic Immunodeficiency, Freiburg University

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs267608259; hg19: chr6-83888399;