Variant 1-11501113-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020780.2(DISP3):c.121G>A(p.Gly41Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,613,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

DISP3
NM_020780.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

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 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=0.03288448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISP3	NM_020780.2 linkuse as main transcript	c.121G>A	p.Gly41Arg	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 linkuse as main transcript	c.121G>A	p.Gly41Arg	missense_variant	2/21	1	NM_020780.2	ENSP00000294484.6		Q9P2K9-1
ENSG00000285833	ENST00000649975.1 linkuse as main transcript	n.741C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000173

AC:

AN:

249052

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

135136

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000511

Gnomad NFE exome

AF:

0.000275

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000120

AC:

176

AN:

1461686

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000431

Gnomad4 NFE exome

AF:

0.000130

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000184

Hom.:

Bravo

AF:

0.0000491

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000174

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000415

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

Oct 05, 2021

The c.121G>A (p.G41R) alteration is located in exon 2 (coding exon 1) of the DISP3 gene. This alteration results from a G to A substitution at nucleotide position 121, causing the glycine (G) at amino acid position 41 to be replaced by an arginine (R). 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

0.081

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.7

DANN

Benign

0.75

DEOGEN2

Benign

0.0059

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.59

M_CAP

Benign

0.0040

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.46

REVEL

Benign

0.12

Sift

Benign

0.51

Sift4G

Benign

0.55

Polyphen

0.0

Vest4

0.24

MutPred

0.27

Gain of MoRF binding (P = 0.0143);

MVP

0.21

MPC

0.66

ClinPred

0.018

GERP RS

3.3

Varity_R

0.045

gMVP

0.39

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