NM_015018.4:c.1426G>A

Variant names:

• chr6-83124790-G-A
• NM_015018.4:c.1426G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015018.4(DOP1A):​c.1426G>A​(p.Val476Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DOP1A NM_015018.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.31
• Publications: 0 publications found

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]

DOP1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40356317).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015018.4. 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
	DOP1A	NM_015018.4	MANE Select	c.1426G>A	p.Val476Met	missense	Exon 13 of 39	NP_055833.2
	DOP1A	NM_001385864.1		c.-81G>A		5_prime_UTR_premature_start_codon_gain	Exon 13 of 38	NP_001372793.1
	DOP1A	NM_001199942.2		c.1399G>A	p.Val467Met	missense	Exon 13 of 40	NP_001186871.1	Q5TA12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOP1A	ENST00000349129.7	TSL:1 MANE Select	c.1426G>A	p.Val476Met	missense	Exon 13 of 39	ENSP00000195654.3	Q5JWR5
	DOP1A	ENST00000369739.7	TSL:1	c.1399G>A	p.Val467Met	missense	Exon 12 of 39	ENSP00000358754.3	Q5TA12
	DOP1A	ENST00000237163.9	TSL:5	c.1399G>A	p.Val467Met	missense	Exon 13 of 40	ENSP00000237163.6	Q5TA12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.044	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.3
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.061	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.49		Loss of stability (P = 0.1438)
MVP		0.082
MPC		0.91
ClinPred		0.93	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.54
Mutation Taster		=63/37	polymorphism

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

hg19: chr6-83834509; COSMIC: COSV52706268;