Variant 1-11501635-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_020780.2(DISP3):c.643G>T(p.Ala215Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00054 in 1,608,942 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 34)

Exomes 𝑓: 0.00031 ( 3 hom. )

Consequence

DISP3
NM_020780.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.774

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053200424).

BP6

Variant 1-11501635-G-T is Benign according to our data. Variant chr1-11501635-G-T is described in ClinVar as [Benign]. Clinvar id is 725514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISP3	NM_020780.2 link	c.643G>T	p.Ala215Ser	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.643G>T	p.Ala215Ser	missense_variant	2/21	1	NM_020780.2	ENSP00000294484.6		Q9P2K9-1
ENSG00000285833	ENST00000649975.1 link	n.382C>A		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

412

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00943

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000599

AC:

141

AN:

235476

Hom.:

AF XY:

0.000517

AC XY:

AN XY:

129480

show subpopulations

Gnomad AFR exome

AF:

0.00924

Gnomad AMR exome

AF:

0.000267

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000528

GnomAD4 exome

AF:

0.000312

AC:

455

AN:

1456586

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

212

AN XY:

724066

show subpopulations

Gnomad4 AFR exome

AF:

0.0111

Gnomad4 AMR exome

AF:

0.000294

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.000782

GnomAD4 genome

AF:

0.00272

AC:

414

AN:

152356

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

194

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00945

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000464

Hom.:

Bravo

AF:

0.00277

ESP6500AA

AF:

0.00708

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000746

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0039

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0053

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.26

REVEL

Benign

0.073

Sift

Benign

0.49

Sift4G

Benign

0.36

Polyphen

0.32

Vest4

0.077

MVP

0.25

MPC

0.38

ClinPred

0.0096

GERP RS

4.9

Varity_R

0.044

gMVP

0.48

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