6-83166527-AAAAT-A

Variant summary

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

The NM_015599.3(PGM3):c.*2703_*2706del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 684,910 control chromosomes in the GnomAD database, including 370 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (150 hom., cov: 32)
  • Exomes 𝑓: 0.012 (220 hom.)
• Consequence: PGM3 NM_015599.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.347

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 6-83166527-AAAAT-A is Benign according to our data. Variant chr6-83166527-AAAAT-A is described in ClinVar as [Benign]. Clinvar id is 1175579.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGM3	NM_015599.3	c.*2703_*2706del		3_prime_UTR_variant	13/13	ENST00000513973.6
DOP1A	NM_015018.4	c.7093-1329_7093-1326del		intron_variant		ENST00000349129.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGM3	ENST00000513973.6	c.*2703_*2706del		3_prime_UTR_variant	13/13	1	NM_015599.3	P1
DOP1A	ENST00000349129.7	c.7093-1329_7093-1326del		intron_variant		1	NM_015018.4	P4

Frequencies

GnomAD3 genomes AF: 0.0285 AC: 4333 AN: 152164 Hom.: 146 Cov.: 32

Gnomad AFR AF: 0.0775

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0827

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.0225

GnomAD4 exome AF: 0.0119 AC: 6353 AN: 532628 Hom.: 220 AF XY: 0.0123 AC XY: 3512 AN XY: 286470

Gnomad4 AFR exome AF: 0.0814

Gnomad4 AMR exome AF: 0.0139

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0662

Gnomad4 SAS exome AF: 0.0318

Gnomad4 FIN exome AF: 0.000430

Gnomad4 NFE exome AF: 0.000968

Gnomad4 OTH exome AF: 0.0147

GnomAD4 genome AF: 0.0285 AC: 4347 AN: 152282 Hom.: 150 Cov.: 32 AF XY: 0.0289 AC XY: 2152 AN XY: 74466

Gnomad4 AFR AF: 0.0776

Gnomad4 AMR AF: 0.0265

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0827

Gnomad4 SAS AF: 0.0363

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0160 Hom.: 10

Bravo AF: 0.0316

Asia WGS AF: 0.0630 AC: 218 AN: 3478

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

Jul 30, 2020

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Computational scores

Source: dbNSFP v4.3

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: rs150637901; hg19: chr6-83876246;