9-68357096-G-A

Position:

• chr9-68357096-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021965.4(PGM5):​c.-32G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,444,862 control chromosomes in the GnomAD database, including 116,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11632 hom., cov: 31)
  • Exomes 𝑓: 0.40 (104911 hom.)
• Consequence: PGM5 NM_021965.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.36

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]

PGM5-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-68357096-G-A is Benign according to our data. Variant chr9-68357096-G-A is described in ClinVar as [Benign]. Clinvar id is 1278897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGM5	NM_021965.4	c.-32G>A		5_prime_UTR_variant	1/11	ENST00000396396.6	NP_068800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGM5	ENST00000396396.6	c.-32G>A		5_prime_UTR_variant	1/11	2	NM_021965.4	ENSP00000379678.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58953 AN: 151378 Hom.: 11621 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.412

GnomAD3 exomes AF: 0.417 AC: 27101 AN: 64932 Hom.: 5820 AF XY: 0.415 AC XY: 14394 AN XY: 34678

Gnomad AFR exome AF: 0.384

Gnomad AMR exome AF: 0.500

Gnomad ASJ exome AF: 0.436

Gnomad EAS exome AF: 0.341

Gnomad SAS exome AF: 0.351

Gnomad FIN exome AF: 0.449

Gnomad NFE exome AF: 0.414

Gnomad OTH exome AF: 0.422

GnomAD4 exome AF: 0.401 AC: 519251 AN: 1293376 Hom.: 104911 Cov.: 34 AF XY: 0.400 AC XY: 252209 AN XY: 630290

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.484

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.293

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.431

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.407

GnomAD4 genome AF: 0.390 AC: 59007 AN: 151486 Hom.: 11632 Cov.: 31 AF XY: 0.389 AC XY: 28798 AN XY: 73994

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.405

Gnomad4 OTH AF: 0.418

Alfa AF: 0.388 Hom.: 1592

Bravo AF: 0.393

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 25, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.8
DANN	Benign	0.91

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: rs10867824; hg19: chr9-70972012;