Variant chr1-11501143-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020780.2(DISP3):c.151C>G(p.Leu51Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,613,926 control chromosomes in the GnomAD database, including 19 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 (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0013 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 15 hom. )

Consequence

DISP3
NM_020780.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.104

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027417839).

BP6

Variant 1-11501143-C-G is Benign according to our data. Variant chr1-11501143-C-G is described in ClinVar as [Benign]. Clinvar id is 721203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00133 (203/152288) while in subpopulation EAS AF= 0.0244 (126/5162). AF 95% confidence interval is 0.0209. There are 4 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISP3	NM_020780.2 link	c.151C>G	p.Leu51Val	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.151C>G	p.Leu51Val	missense_variant	2/21	1	NM_020780.2	ENSP00000294484.6		Q9P2K9-1
ENSG00000285833	ENST00000649975.1 link	n.711G>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

203

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.0244

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00351

AC:

873

AN:

248574

Hom.:

AF XY:

0.00309

AC XY:

417

AN XY:

134912

show subpopulations

Gnomad AFR exome

AF:

0.000583

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.00340

Gnomad EAS exome

AF:

0.0237

Gnomad SAS exome

AF:

0.000556

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000533

Gnomad OTH exome

AF:

0.00232

GnomAD4 exome

AF:

0.00106

AC:

1547

AN:

1461638

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

739

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00888

Gnomad4 ASJ exome

AF:

0.00257

Gnomad4 EAS exome

AF:

0.0228

Gnomad4 SAS exome

AF:

0.000499

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.00133

AC:

203

AN:

152288

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

107

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.0244

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000893

Hom.:

Bravo

AF:

0.00197

ExAC

AF:

0.00309

AC:

373

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

DISP3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 13, 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

0.067

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.65

CADD

Benign

4.3

DANN

Benign

0.90

DEOGEN2

Benign

0.0070

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.81

REVEL

Benign

0.017

Sift

Benign

0.042

Sift4G

Benign

0.19

Polyphen

0.18

Vest4

0.13

MVP

0.076

MPC

0.55

ClinPred

0.0059

GERP RS

-1.7

Varity_R

0.069

gMVP

0.18

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