6-83166558-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015599.3(PGM3):c.*2675del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0173 in 575,702 control chromosomes in the GnomAD database, including 327 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (156 hom., cov: 32)
  • Exomes 𝑓: 0.013 (171 hom.)
• Consequence: PGM3 NM_015599.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.230

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 6-83166558-CA-C is Benign according to our data. Variant chr6-83166558-CA-C is described in ClinVar as [Benign]. Clinvar id is 1240948.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGM3	NM_015599.3	c.*2675del		3_prime_UTR_variant	13/13	ENST00000513973.6
DOP1A	NM_015018.4	c.7093-1295del		intron_variant		ENST00000349129.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGM3	ENST00000513973.6	c.*2675del		3_prime_UTR_variant	13/13	1	NM_015599.3	P1
DOP1A	ENST00000349129.7	c.7093-1295del		intron_variant		1	NM_015018.4	P4

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4351 AN: 149542 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.0789

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0849

Gnomad SAS AF: 0.0368

Gnomad FIN AF: 0.000608

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.000817

Gnomad OTH AF: 0.0240

GnomAD4 exome AF: 0.0132 AC: 5604 AN: 426048 Hom.: 171 Cov.: 6 AF XY: 0.0133 AC XY: 2972 AN XY: 224162

Gnomad4 AFR exome AF: 0.0881

Gnomad4 AMR exome AF: 0.0199

Gnomad4 ASJ exome AF: 0.000773

Gnomad4 EAS exome AF: 0.0688

Gnomad4 SAS exome AF: 0.0359

Gnomad4 FIN exome AF: 0.00112

Gnomad4 NFE exome AF: 0.00229

Gnomad4 OTH exome AF: 0.0162

GnomAD4 genome AF: 0.0292 AC: 4363 AN: 149654 Hom.: 156 Cov.: 32 AF XY: 0.0295 AC XY: 2152 AN XY: 72958

Gnomad4 AFR AF: 0.0790

Gnomad4 AMR AF: 0.0272

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0849

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.000608

Gnomad4 NFE AF: 0.000817

Gnomad4 OTH AF: 0.0247

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 13, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs368890859; hg19: chr6-83876277;