Variant 1-11501536-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_020780.2(DISP3):c.544G>A(p.Gly182Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,593,124 control chromosomes in the GnomAD database, including 285,773 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.49 ( 21360 hom., cov: 33)

Exomes 𝑓: 0.60 ( 264413 hom. )

Consequence

DISP3
NM_020780.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.571

Variant links:

Genes affected

DISP3 (HGNC:29251): (dispatched RND transporter family member 3) Involved in negative regulation of neuron differentiation; positive regulation of lipid metabolic process; and positive regulation of neural precursor cell proliferation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DISP3 links:

ENSG00000285833 (HGNC:):

ENSG00000285833 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6648062E-5).

BP6

Variant 1-11501536-G-A is Benign according to our data. Variant chr1-11501536-G-A is described in ClinVar as [Benign]. Clinvar id is 3060301.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISP3	NM_020780.2 link	c.544G>A	p.Gly182Ser	missense_variant	2/21	ENST00000294484.7	NP_065831.1	Q9P2K9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISP3	ENST00000294484.7 link	c.544G>A	p.Gly182Ser	missense_variant	2/21	1	NM_020780.2	ENSP00000294484.6		Q9P2K9-1
ENSG00000285833	ENST00000649975.1 link	n.466+15C>T		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.495

AC:

75230

AN:

151976

Hom.:

21349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.678

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.630

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.638

Gnomad OTH

AF:

0.508

GnomAD3 exomes

AF:

0.549

AC:

125195

AN:

228176

Hom.:

37178

AF XY:

0.545

AC XY:

68162

AN XY:

125054

show subpopulations

Gnomad AFR exome

AF:

0.209

Gnomad AMR exome

AF:

0.664

Gnomad ASJ exome

AF:

0.556

Gnomad EAS exome

AF:

0.278

Gnomad SAS exome

AF:

0.358

Gnomad FIN exome

AF:

0.636

Gnomad NFE exome

AF:

0.637

Gnomad OTH exome

AF:

0.593

GnomAD4 exome

AF:

0.595

AC:

858021

AN:

1441030

Hom.:

264413

Cov.:

AF XY:

0.589

AC XY:

421066

AN XY:

715172

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.660

Gnomad4 ASJ exome

AF:

0.557

Gnomad4 EAS exome

AF:

0.247

Gnomad4 SAS exome

AF:

0.365

Gnomad4 FIN exome

AF:

0.637

Gnomad4 NFE exome

AF:

0.636

Gnomad4 OTH exome

AF:

0.563

GnomAD4 genome

AF:

0.495

AC:

75254

AN:

152094

Hom.:

21360

Cov.:

AF XY:

0.491

AC XY:

36500

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.610

Gnomad4 ASJ

AF:

0.551

Gnomad4 EAS

AF:

0.271

Gnomad4 SAS

AF:

0.343

Gnomad4 FIN

AF:

0.630

Gnomad4 NFE

AF:

0.638

Gnomad4 OTH

AF:

0.507

Alfa

AF:

0.616

Hom.:

20776

Bravo

AF:

0.487

TwinsUK

AF:

0.631

AC:

2340

ALSPAC

AF:

0.623

AC:

2402

ESP6500AA

AF:

0.252

AC:

960

ESP6500EA

AF:

0.634

AC:

5214

ExAC

AF:

0.534

AC:

64244

Asia WGS

AF:

0.286

AC:

995

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DISP3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.0

DANN

Benign

0.96

DEOGEN2

Benign

0.012

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.54

MetaRNN

Benign

0.000017

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.31

REVEL

Benign

0.0060

Sift

Benign

1.0

Sift4G

Benign

0.85

Polyphen

0.0080

Vest4

0.024

MPC

0.37

ClinPred

0.014

GERP RS

0.79

Varity_R

0.021

gMVP

0.55

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