9-68357096-G-T

Variant names:

• chr9-68357096-G-T
• rs10867824
• NM_021965.4:c.-32G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021965.4(PGM5):​c.-32G>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PGM5 NM_021965.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.36
• Publications: 3 publications found

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:44181): (PGM5 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021965.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM5	NM_021965.4	MANE Select	c.-32G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_068800.2	Q15124-1
	PGM5	NM_021965.4	MANE Select	c.-32G>T		5_prime_UTR	Exon 1 of 11	NP_068800.2	Q15124-1
	PGM5-AS1	NR_015423.2		n.144+627C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM5	ENST00000396396.6	TSL:2 MANE Select	c.-32G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000379678.1	Q15124-1
	PGM5	ENST00000396392.5	TSL:1	c.-32G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000379674.1	Q15124-2
	PGM5	ENST00000396396.6	TSL:2 MANE Select	c.-32G>T		5_prime_UTR	Exon 1 of 11	ENSP00000379678.1	Q15124-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.73e-7 AC: 1 AN: 1294432 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 630768

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26894

American (AMR) AF: 0.00 AC: 0 AN: 23894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19754

East Asian (EAS) AF: 0.00 AC: 0 AN: 32286

South Asian (SAS) AF: 0.00 AC: 0 AN: 65898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3700

European-Non Finnish (NFE) AF: 9.64e-7 AC: 1 AN: 1036978

Other (OTH) AF: 0.00 AC: 0 AN: 53778

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1592

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.78
PhyloP100		-4.4
PromoterAI		-0.074	Neutral

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

Other links and lift over

dbSNP: rs10867824; hg19: chr9-70972012;