Genetic Variant PGM3:c.*2675dupT (chr6-83166558-C-CA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015599.3(PGM3):c.*2675dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000456 in 577,274 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000073 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 0 hom. )

Consequence

PGM3
NM_015599.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

0 publications found

Variant links:

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]

PGM3 links:

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

DOP1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PGM3	NM_015599.3	MANE Select	c.*2675dupT	3_prime_UTR	Exon 13 of 13	NP_056414.1	O95394-1
DOP1A	NM_015018.4	MANE Select	c.7093-1295dupA	intron	N/A	NP_055833.2
PGM3	NM_001199917.2		c.*2675dupT	3_prime_UTR	Exon 14 of 14	NP_001186846.1	O95394-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PGM3	ENST00000513973.6	TSL:1 MANE Select	c.*2675dupT	3_prime_UTR	Exon 13 of 13	ENSP00000424874.1	O95394-1
DOP1A	ENST00000349129.7	TSL:1 MANE Select	c.7093-1295dupA	intron	N/A	ENSP00000195654.3	Q5JWR5
DOP1A	ENST00000369739.7	TSL:1	c.7126-1295dupA	intron	N/A	ENSP00000358754.3	Q5TA12

Frequencies

GnomAD3 genomes

AF:

0.0000736

AC:

AN:

149554

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000391

Gnomad SAS

AF:

0.000421

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000104

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000589

AC:

252

AN:

427608

Hom.:

Cov.:

AF XY:

0.000627

AC XY:

141

AN XY:

225020

show subpopulations

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

African (AFR)

AF:

0.000593

AC:

AN:

11798

American (AMR)

AF:

0.000847

AC:

AN:

17704

Ashkenazi Jewish (ASJ)

AF:

0.000350

AC:

AN:

14300

East Asian (EAS)

AF:

0.000739

AC:

AN:

28410

South Asian (SAS)

AF:

0.000937

AC:

AN:

33078

European-Finnish (FIN)

AF:

0.000144

AC:

AN:

27724

Middle Eastern (MID)

AF:

0.000291

AC:

AN:

3438

European-Non Finnish (NFE)

AF:

0.000589

AC:

157

AN:

266510

Other (OTH)

AF:

0.000446

AC:

AN:

24646

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.272

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000735

AC:

AN:

149666

Hom.:

Cov.:

AF XY:

0.0000685

AC XY:

AN XY:

72968

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40846

American (AMR)

AF:

0.00

AC:

AN:

15046

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.000392

AC:

AN:

5104

South Asian (SAS)

AF:

0.000421

AC:

AN:

4748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9866

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000104

AC:

AN:

67342

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000543

Hom.:

Bravo

AF:

0.0000869

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

6-83166558-CAA-CAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over