dbSNP rs773502955: DOP1A:p.Ile631Thr (chr6-83129059-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015018.4(DOP1A):c.1892T>C(p.Ile631Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

DOP1A
NM_015018.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053626448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOP1A	NM_015018.4 link	c.1892T>C	p.Ile631Thr	missense_variant	Exon 16 of 39	ENST00000349129.7	NP_055833.2	Q5JWR5B2RWN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DOP1A	ENST00000349129.7 link	c.1892T>C	p.Ile631Thr	missense_variant	Exon 16 of 39	1	NM_015018.4	ENSP00000195654.3	Q5JWR5
DOP1A	ENST00000369739.7 link	c.1865T>C	p.Ile622Thr	missense_variant	Exon 15 of 39	1		ENSP00000358754.3	Q5TA12
DOP1A	ENST00000237163.9 link	c.1865T>C	p.Ile622Thr	missense_variant	Exon 16 of 40	5		ENSP00000237163.6	Q5TA12
DOP1A	ENST00000604380.1 link	c.*131T>C		downstream_gene_variant		5		ENSP00000474846.1	S4R3Y1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250754

Hom.:

AF XY:

0.0000517

AC XY:

AN XY:

135476

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461780

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727176

show subpopulations

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:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1865T>C (p.I622T) alteration is located in exon 16 (coding exon 14) of the DOPEY1 gene. This alteration results from a T to C substitution at nucleotide position 1865, causing the isoleucine (I) at amino acid position 622 to be replaced by a threonine (T). 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

Benign

0.062

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.0083

.;T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.73

T;T;.

M_CAP

Benign

0.0063

MetaRNN

Benign

0.054

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

.;L;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.21

.;N;.

REVEL

Benign

0.038

Sift

Benign

0.19

.;T;.

Sift4G

Benign

0.45

T;T;T

Polyphen

0.10

.;B;.

Vest4

0.21

MutPred

0.16

.;Gain of glycosylation at I631 (P = 0.0043);.;

MVP

0.043

MPC

0.32

ClinPred

0.033

GERP RS

3.5

Varity_R

0.067

gMVP

0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over