6-83166558-CA-C

Variant names:

• chr6-83166558-CA-C
• rs368890859
• NM_015599.3:c.*2675delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015599.3(PGM3):​c.*2675delT 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
• Publications: 0 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 -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 VariationId 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.

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.*2675delT		3_prime_UTR	Exon 13 of 13	NP_056414.1	O95394-1
	DOP1A	NM_015018.4	MANE Select	c.7093-1295delA		intron	N/A	NP_055833.2
	PGM3	NM_001199917.2		c.*2675delT		3_prime_UTR	Exon 14 of 14	NP_001186846.1	O95394-4

Ensembl Transcripts

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

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

African (AFR) AF: 0.0881 AC: 1035 AN: 11754

American (AMR) AF: 0.0199 AC: 351 AN: 17598

Ashkenazi Jewish (ASJ) AF: 0.000773 AC: 11 AN: 14234

East Asian (EAS) AF: 0.0688 AC: 1948 AN: 28316

South Asian (SAS) AF: 0.0359 AC: 1180 AN: 32900

European-Finnish (FIN) AF: 0.00112 AC: 31 AN: 27646

Middle Eastern (MID) AF: 0.0120 AC: 41 AN: 3422

European-Non Finnish (NFE) AF: 0.00229 AC: 609 AN: 265582

Other (OTH) AF: 0.0162 AC: 398 AN: 24596

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

African (AFR) AF: 0.0790 AC: 3225 AN: 40838

American (AMR) AF: 0.0272 AC: 410 AN: 15046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.0849 AC: 433 AN: 5102

South Asian (SAS) AF: 0.0369 AC: 175 AN: 4748

European-Finnish (FIN) AF: 0.000608 AC: 6 AN: 9864

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.000817 AC: 55 AN: 67344

Other (OTH) AF: 0.0247 AC: 51 AN: 2066

Alfa AF: 0.0000543 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs368890859; hg19: chr6-83876277;