NM_015599.3:c.1464C>T

Variant names:

• chr6-83170380-G-A
• rs34873318
• NM_015599.3:c.1464C>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_015599.3(PGM3):​c.1464C>T​(p.Tyr488Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00329 in 1,614,108 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (87 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (58 hom.)
• Consequence: PGM3 NM_015599.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.46
• Publications: 2 publications found

Genes affected

PGM3 (HGNC:8907): (phosphoglucomutase 3) This gene encodes a member of the phosphohexose mutase family. The encoded protein mediates both glycogen formation and utilization by catalyzing the interconversion of glucose-1-phosphate and glucose-6-phosphate. A non-synonymous single nucleotide polymorphism in this gene may play a role in resistance to diabetic nephropathy and neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

DOP1A (HGNC:21194): (DOP1 leucine zipper like protein A) Predicted to be involved in Golgi to endosome transport and endoplasmic reticulum organization. Predicted to be located in Golgi membrane. Predicted to be active in endosome and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

DOP1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 6-83170380-G-A is Benign according to our data. Variant chr6-83170380-G-A is described in ClinVar as Benign. ClinVar VariationId is 475001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015599.3. 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
	PGM3	NM_015599.3	MANE Select	c.1464C>T	p.Tyr488Tyr	synonymous	Exon 12 of 13	NP_056414.1	O95394-1
	PGM3	NM_001199917.2		c.1548C>T	p.Tyr516Tyr	synonymous	Exon 13 of 14	NP_001186846.1	O95394-4
	PGM3	NM_001367287.1		c.1548C>T	p.Tyr516Tyr	synonymous	Exon 13 of 14	NP_001354216.1	O95394-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGM3	ENST00000513973.6	TSL:1 MANE Select	c.1464C>T	p.Tyr488Tyr	synonymous	Exon 12 of 13	ENSP00000424874.1	O95394-1
	PGM3	ENST00000512866.5	TSL:1	c.1464C>T	p.Tyr488Tyr	synonymous	Exon 12 of 14	ENSP00000421565.1	O95394-3
	PGM3	ENST00000283977.9	TSL:5	c.1221C>T	p.Tyr407Tyr	synonymous	Exon 11 of 12	ENSP00000283977.5	J3KN95

Frequencies

GnomAD3 genomes AF: 0.0168 AC: 2552 AN: 152154 Hom.: 86 Cov.: 33

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0125

GnomAD2 exomes AF: 0.00445 AC: 1120 AN: 251426 AF XY: 0.00325

Gnomad AFR exome AF: 0.0560

Gnomad AMR exome AF: 0.00385

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000431

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00188 AC: 2746 AN: 1461836 Hom.: 58 Cov.: 30 AF XY: 0.00162 AC XY: 1179 AN XY: 727222

African (AFR) AF: 0.0567 AC: 1898 AN: 33474

American (AMR) AF: 0.00429 AC: 192 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00138 AC: 36 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00624 AC: 36 AN: 5768

European-Non Finnish (NFE) AF: 0.000255 AC: 283 AN: 1111974

Other (OTH) AF: 0.00487 AC: 294 AN: 60392

GnomAD4 genome AF: 0.0168 AC: 2565 AN: 152272 Hom.: 87 Cov.: 33 AF XY: 0.0165 AC XY: 1229 AN XY: 74454

African (AFR) AF: 0.0577 AC: 2398 AN: 41548

American (AMR) AF: 0.00700 AC: 107 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68024

Other (OTH) AF: 0.0123 AC: 26 AN: 2108

Alfa AF: 0.00663 Hom.: 10

Bravo AF: 0.0188

Asia WGS AF: 0.00577 AC: 21 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000830

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Immunodeficiency 23 (1)
-	-	1	not provided (1)
-	-	1	PGM3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.5
DANN	Benign	0.83
PhyloP100		2.5
Mutation Taster		=98/2	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: rs34873318; hg19: chr6-83880099;