chr6-83166527-AAAAT-A

Variant names:

• chr6-83166527-AAAAT-A
• rs150637901
• NM_015599.3:c.*2703_*2706delATTT

Variant summary

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

The NM_015599.3(PGM3):​c.*2703_*2706delATTT 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
• Publications: 1 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 6-83166527-AAAAT-A is Benign according to our data. Variant chr6-83166527-AAAAT-A is described in ClinVar as Benign. ClinVar VariationId 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.

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.*2703_*2706delATTT		3_prime_UTR	Exon 13 of 13	NP_056414.1	O95394-1
	DOP1A	NM_015018.4	MANE Select	c.7093-1329_7093-1326delAATA		intron	N/A	NP_055833.2
	PGM3	NM_001199917.2		c.*2703_*2706delATTT		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.*2703_*2706delATTT		3_prime_UTR	Exon 13 of 13	ENSP00000424874.1	O95394-1
	DOP1A	ENST00000349129.7	TSL:1 MANE Select	c.7093-1329_7093-1326delAATA		intron	N/A	ENSP00000195654.3	Q5JWR5
	DOP1A	ENST00000369739.7	TSL:1	c.7126-1329_7126-1326delAATA		intron	N/A	ENSP00000358754.3	Q5TA12

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

African (AFR) AF: 0.0814 AC: 1216 AN: 14944

American (AMR) AF: 0.0139 AC: 430 AN: 30840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19102

East Asian (EAS) AF: 0.0662 AC: 2097 AN: 31698

South Asian (SAS) AF: 0.0318 AC: 1811 AN: 56878

European-Finnish (FIN) AF: 0.000430 AC: 14 AN: 32590

Middle Eastern (MID) AF: 0.0112 AC: 44 AN: 3942

European-Non Finnish (NFE) AF: 0.000968 AC: 303 AN: 312874

Other (OTH) AF: 0.0147 AC: 438 AN: 29760

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

African (AFR) AF: 0.0776 AC: 3225 AN: 41554

American (AMR) AF: 0.0265 AC: 406 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0827 AC: 428 AN: 5174

South Asian (SAS) AF: 0.0363 AC: 175 AN: 4820

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10618

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

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68028

Other (OTH) AF: 0.0232 AC: 49 AN: 2114

Alfa AF: 0.0160 Hom.: 10

Bravo AF: 0.0316

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

ClinVar submissions

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		0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs150637901; hg19: chr6-83876246;