Variant 1-93360632-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001938.3(DR1):c.524A>G(p.Asp175Gly) 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DR1
NM_001938.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.43

Variant links:

Genes affected

DR1 (HGNC:3017): (down-regulator of transcription 1) This gene encodes a TBP- (TATA box-binding protein) associated phosphoprotein that represses both basal and activated levels of transcription. The encoded protein is phosphorylated in vivo and this phosphorylation affects its interaction with TBP. This protein contains a histone fold motif at the amino terminus, a TBP-binding domain, and a glutamine- and alanine-rich region. The binding of DR1 repressor complexes to TBP-promoter complexes may establish a mechanism in which an altered DNA conformation, together with the formation of higher order complexes, inhibits the assembly of the preinitiation complex and controls the rate of RNA polymerase II transcription. [provided by RefSeq, Jul 2008]

DR1 links:

DR1 (HGNC:):

DR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DR1	NM_001938.3 linkuse as main transcript	c.524A>G	p.Asp175Gly	missense_variant	3/3	ENST00000370272.9	NP_001929.1	Q01658Q658N3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DR1	ENST00000370272.9 linkuse as main transcript	c.524A>G	p.Asp175Gly	missense_variant	3/3	1	NM_001938.3	ENSP00000359295.3	Q01658
DR1	ENST00000481583.1 linkuse as main transcript	n.941A>G		non_coding_transcript_exon_variant	2/2	1
DR1	ENST00000370267.1 linkuse as main transcript	c.524A>G	p.Asp175Gly	missense_variant	4/4	2		ENSP00000359290.1	Q01658

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1431502

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711536

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2023

The c.524A>G (p.D175G) alteration is located in exon 3 (coding exon 3) of the DR1 gene. This alteration results from a A to G substitution at nucleotide position 524, causing the aspartic acid (D) at amino acid position 175 to be replaced by a glycine (G). 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

0.24

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.078

T;T

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.64

.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

L;L

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.89

N;N

REVEL

Benign

0.24

Sift

Uncertain

0.013

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

0.10

B;B

Vest4

0.50

MutPred

0.10

Loss of stability (P = 0.0946);Loss of stability (P = 0.0946);

MVP

0.53

MPC

1.3

ClinPred

0.85

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.5

Varity_R

0.25

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.30

Position offset: -1

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