6-83155954-G-C

Variant names:

• chr6-83155954-G-C
• NM_015018.4:c.6455G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015018.4(DOP1A):​c.6455G>C​(p.Arg2152Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DOP1A NM_015018.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.57

Genes affected

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOP1A	NM_015018.4	c.6455G>C	p.Arg2152Pro	missense_variant	Exon 34 of 39	ENST00000349129.7	NP_055833.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOP1A	ENST00000349129.7	c.6455G>C	p.Arg2152Pro	missense_variant	Exon 34 of 39	1	NM_015018.4	ENSP00000195654.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457696 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724884

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	.;T;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;.
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Pathogenic	2.9	.;M;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.2	.;D;.
REVEL	Uncertain	0.54
Sift	Uncertain	0.0020	.;D;.
Sift4G	Benign	0.068	T;T;T
Polyphen		1.0	.;D;.
Vest4		0.82
MutPred		0.72		.;Loss of MoRF binding (P = 0.0546);.;
MVP		0.59
MPC		3.1
ClinPred		0.98	D
GERP RS		6.0
Varity_R		0.80
gMVP		0.95

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-83865673;