9-68378237-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_021965.4(PGM5):c.300G>A(p.Ser100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00555 in 1,561,640 control chromosomes in the GnomAD database, including 396 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.031 (210 hom., cov: 27)
  • Exomes 𝑓: 0.0031 (186 hom.)
• Consequence: PGM5 NM_021965.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.520

Genes affected

PGM5 (HGNC:8908): (phosphoglucomutase 5) Phosphoglucomutases (EC 5.2.2.2.), such as PGM5, are phosphotransferases involved in interconversion of glucose-1-phosphate and glucose-6-phosphate. PGM activity is essential in formation of carbohydrates from glucose-6-phosphate and in formation of glucose-6-phosphate from galactose and glycogen (Edwards et al., 1995 [PubMed 8586438]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 9-68378237-G-A is Benign according to our data. Variant chr9-68378237-G-A is described in ClinVar as [Benign]. Clinvar id is 778427.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.52 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGM5	NM_021965.4	c.300G>A	p.Ser100=	synonymous_variant	2/11	ENST00000396396.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGM5	ENST00000396396.6	c.300G>A	p.Ser100=	synonymous_variant	2/11	2	NM_021965.4	P1
PGM5	ENST00000396392.5	c.300G>A	p.Ser100=	synonymous_variant	2/8	1
PGM5	ENST00000431583.1	c.198G>A	p.Ser66=	synonymous_variant	2/4	5
PGM5	ENST00000604870.6	n.655G>A		non_coding_transcript_exon_variant	5/12	5

Frequencies

GnomAD3 genomes AF: 0.0305 AC: 4319 AN: 141708 Hom.: 211 Cov.: 27

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0178

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000207

Gnomad SAS AF: 0.000450

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00658

Gnomad NFE AF: 0.000340

Gnomad OTH AF: 0.0180

GnomAD3 exomes AF: 0.00822 AC: 1765 AN: 214618 Hom.: 79 AF XY: 0.00621 AC XY: 722 AN XY: 116332

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.00730

Gnomad ASJ exome AF: 0.000412

Gnomad EAS exome AF: 0.000120

Gnomad SAS exome AF: 0.000253

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000378

Gnomad OTH exome AF: 0.00400

GnomAD4 exome AF: 0.00306 AC: 4343 AN: 1419834 Hom.: 186 Cov.: 32 AF XY: 0.00264 AC XY: 1864 AN XY: 705294

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.00744

Gnomad4 ASJ exome AF: 0.0000827

Gnomad4 EAS exome AF: 0.0000515

Gnomad4 SAS exome AF: 0.000294

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000414

Gnomad4 OTH exome AF: 0.00738

GnomAD4 genome AF: 0.0305 AC: 4331 AN: 141806 Hom.: 210 Cov.: 27 AF XY: 0.0301 AC XY: 2074 AN XY: 68810

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0178

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000207

Gnomad4 SAS AF: 0.000450

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000340

Gnomad4 OTH AF: 0.0178

Alfa AF: 0.0159 Hom.: 22

Bravo AF: 0.0345

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 04, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	0.17
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs150515274; hg19: chr9-70993153; COSMIC: COSV67163690;