Genetic Variant PGM3:c.*2674_*2675delTT (chr6-83166558-CAA-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015599.3(PGM3):c.*2674_*2675delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000519 in 578,000 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 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

PGM3
NM_015599.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.347

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.2674_2675delTT	3_prime_UTR	Exon 13 of 13	NP_056414.1	O95394-1
DOP1A	NM_015018.4	MANE Select	c.7093-1296_7093-1295delAA	intron	N/A	NP_055833.2
PGM3	NM_001199917.2		c.2674_2675delTT	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.2674_2675delTT	3_prime_UTR	Exon 13 of 13	ENSP00000424874.1	O95394-1
DOP1A	ENST00000349129.7	TSL:1 MANE Select	c.7093-1296_7093-1295delAA	intron	N/A	ENSP00000195654.3	Q5JWR5
DOP1A	ENST00000369739.7	TSL:1	c.7126-1296_7126-1295delAA	intron	N/A	ENSP00000358754.3	Q5TA12

Frequencies

GnomAD3 genomes

AF:

0.00000669

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:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000467

AC:

AN:

428446

Hom.:

AF XY:

0.00000887

AC XY:

AN XY:

225450

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11820

American (AMR)

AF:

0.00

AC:

AN:

17738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14324

East Asian (EAS)

AF:

0.00

AC:

AN:

28440

South Asian (SAS)

AF:

0.0000301

AC:

AN:

33186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27772

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3438

European-Non Finnish (NFE)

AF:

0.00000374

AC:

AN:

267036

Other (OTH)

AF:

0.00

AC:

AN:

24692

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000669

AC:

AN:

149554

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72846

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40728

American (AMR)

AF:

0.00

AC:

AN:

15028

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5116

South Asian (SAS)

AF:

0.000210

AC:

AN:

4752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9864

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67352

Other (OTH)

AF:

0.00

AC:

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over