NM_021965.4:c.366C>T

Variant names:

• chr9-68378303-C-T
• rs147720326
• NM_021965.4:c.366C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_021965.4(PGM5):​c.366C>T​(p.Ser122Ser) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.498
• Publications: 2 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]

ENSG00000233178 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 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 VariationId is 770581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

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.366C>T	p.Ser122Ser	synonymous	Exon 2 of 11	NP_068800.2	Q15124-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM5	ENST00000396396.6	TSL:2 MANE Select	c.366C>T	p.Ser122Ser	synonymous	Exon 2 of 11	ENSP00000379678.1	Q15124-1
	PGM5	ENST00000396392.5	TSL:1	c.366C>T	p.Ser122Ser	synonymous	Exon 2 of 8	ENSP00000379674.1	Q15124-2
	PGM5	ENST00000902469.1		c.366C>T	p.Ser122Ser	synonymous	Exon 2 of 12	ENSP00000572528.1

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

GnomAD2 exomes AF: 0.0333 AC: 7626 AN: 229238 AF XY: 0.0335

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 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

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

African (AFR) AF: 0.0517 AC: 1665 AN: 32182

American (AMR) AF: 0.0190 AC: 782 AN: 41158

Ashkenazi Jewish (ASJ) AF: 0.0329 AC: 841 AN: 25558

East Asian (EAS) AF: 0.0153 AC: 598 AN: 38978

South Asian (SAS) AF: 0.0177 AC: 1491 AN: 84246

European-Finnish (FIN) AF: 0.0418 AC: 2187 AN: 52364

Middle Eastern (MID) AF: 0.0348 AC: 142 AN: 4078

European-Non Finnish (NFE) AF: 0.0441 AC: 48406 AN: 1097348

Other (OTH) AF: 0.0408 AC: 2417 AN: 59206

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

African (AFR) AF: 0.0576 AC: 2364 AN: 41068

American (AMR) AF: 0.0384 AC: 583 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.0332 AC: 115 AN: 3460

East Asian (EAS) AF: 0.00754 AC: 39 AN: 5174

South Asian (SAS) AF: 0.0115 AC: 55 AN: 4774

European-Finnish (FIN) AF: 0.0467 AC: 490 AN: 10498

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0476 AC: 3230 AN: 67862

Other (OTH) AF: 0.0446 AC: 93 AN: 2084

Alfa AF: 0.0422 Hom.: 28

Bravo AF: 0.0487

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.9
DANN	Benign	0.69
PhyloP100		0.50
Mutation Taster		=89/11	polymorphism (auto)

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: rs147720326; hg19: chr9-70993219;