chr6-83124790-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001385864.1(DOP1A):​c.-81G>A variant causes a 5 prime UTR premature start codon gain 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_001385864.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.31

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOP1A	NM_015018.4	c.1426G>A	p.Val476Met	missense_variant	Exon 13 of 39	ENST00000349129.7	NP_055833.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOP1A	ENST00000349129.7	c.1426G>A	p.Val476Met	missense_variant	Exon 13 of 39	1	NM_015018.4	ENSP00000195654.3
DOP1A	ENST00000369739.7	c.1399G>A	p.Val467Met	missense_variant	Exon 12 of 39	1		ENSP00000358754.3
DOP1A	ENST00000237163.9	c.1399G>A	p.Val467Met	missense_variant	Exon 13 of 40	5		ENSP00000237163.6
DOP1A	ENST00000604380.1	c.205G>A	p.Val69Met	missense_variant	Exon 2 of 4	5		ENSP00000474846.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1399G>A (p.V467M) alteration is located in exon 13 (coding exon 11) of the DOPEY1 gene. This alteration results from a G to A substitution at nucleotide position 1399, causing the valine (V) at amino acid position 467 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D;.
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.41	N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0060	D;D;D
Sift4G	Benign	0.061	T;T;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

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: chr6-83834509; COSMIC: COSV52706268;