9-68378303-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_021965.4(PGM5):c.366C>T(p.Ser122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 151,324 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (175 hom., cov: 28)
  • Exomes 𝑓: 0.041 (1246 hom.)
  • Failed GnomAD Quality Control
• Consequence: PGM5 NM_021965.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.498

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 9-68378303-C-T is Benign according to our data. Variant chr9-68378303-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 770581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.498 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGM5	NM_021965.4	c.366C>T	p.Ser122=	synonymous_variant	2/11	ENST00000396396.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGM5	ENST00000396396.6	c.366C>T	p.Ser122=	synonymous_variant	2/11	2	NM_021965.4	P1
PGM5	ENST00000396392.5	c.366C>T	p.Ser122=	synonymous_variant	2/8	1
PGM5	ENST00000431583.1	c.264C>T	p.Ser88=	synonymous_variant	2/4	5
PGM5	ENST00000604870.6	n.721C>T		non_coding_transcript_exon_variant	5/12	5

Frequencies

GnomAD3 genomes AF: 0.0462 AC: 6988 AN: 151206 Hom.: 174 Cov.: 28

Gnomad AFR AF: 0.0573

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0332

Gnomad EAS AF: 0.00752

Gnomad SAS AF: 0.0115

Gnomad FIN AF: 0.0467

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0476

Gnomad OTH AF: 0.0451

GnomAD3 exomes AF: 0.0333 AC: 7626 AN: 229238 Hom.: 128 AF XY: 0.0335 AC XY: 4164 AN XY: 124342

Gnomad AFR exome AF: 0.0553

Gnomad AMR exome AF: 0.0181

Gnomad ASJ exome AF: 0.0277

Gnomad EAS exome AF: 0.00640

Gnomad SAS exome AF: 0.0163

Gnomad FIN exome AF: 0.0424

Gnomad NFE exome AF: 0.0421

Gnomad OTH exome AF: 0.0340

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0408 AC: 58529 AN: 1435118 Hom.: 1246 Cov.: 31 AF XY: 0.0402 AC XY: 28654 AN XY: 713264

Gnomad4 AFR exome AF: 0.0517

Gnomad4 AMR exome AF: 0.0190

Gnomad4 ASJ exome AF: 0.0329

Gnomad4 EAS exome AF: 0.0153

Gnomad4 SAS exome AF: 0.0177

Gnomad4 FIN exome AF: 0.0418

Gnomad4 NFE exome AF: 0.0441

Gnomad4 OTH exome AF: 0.0408

GnomAD4 genome AF: 0.0463 AC: 7003 AN: 151324 Hom.: 175 Cov.: 28 AF XY: 0.0440 AC XY: 3253 AN XY: 73906

Gnomad4 AFR AF: 0.0576

Gnomad4 AMR AF: 0.0384

Gnomad4 ASJ AF: 0.0332

Gnomad4 EAS AF: 0.00754

Gnomad4 SAS AF: 0.0115

Gnomad4 FIN AF: 0.0467

Gnomad4 NFE AF: 0.0476

Gnomad4 OTH AF: 0.0446

Alfa AF: 0.0422 Hom.: 28

Bravo AF: 0.0487

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	9.9
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs147720326; hg19: chr9-70993219;