rs9441940

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001377229.1(DISP1):c.3739G>A(p.Ala1247Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,614,050 control chromosomes in the GnomAD database, including 22,294 homozygotes. 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1247S) has been classified as Benign.

Frequency

Genomes: 𝑓 0.12 ( 1471 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20823 hom. )

Consequence

DISP1
NM_001377229.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.77

Variant links:

Genes affected

DISP1 (HGNC:19711): (dispatched RND transporter family member 1) The pattern of cellular proliferation and differentiation that leads to normal development of embryonic structures often depends upon the localized production of secreted protein signals. Cells surrounding the source of a particular signal respond in a graded manner according to the effective concentration of the signal, and this response produces the pattern of cell types constituting the mature structure. A novel segment-polarity gene known as dispatched has been identified in Drosophila and its protein product is required for normal Hedgehog (Hh) signaling. This gene is one of two human homologs of Drosophila dispatched and, based on sequence identity to its mouse counterpart, the encoded protein may play an essential role in Hh patterning activities in the early embryo. [provided by RefSeq, Jul 2008]

DISP1 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=7.4002147E-4).

BP6

Variant 1-223005136-G-A is Benign according to our data. Variant chr1-223005136-G-A is described in ClinVar as [Benign]. Clinvar id is 811581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISP1	NM_001377229.1 link	c.3739G>A	p.Ala1247Thr	missense_variant	Exon 9 of 9	ENST00000675850.1	NP_001364158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISP1	ENST00000675850.1 link	c.3739G>A	p.Ala1247Thr	missense_variant	Exon 9 of 9		NM_001377229.1	ENSP00000502357.1		Q96F81

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18628

AN:

152068

Hom.:

1471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0397

Gnomad AMI

AF:

0.0670

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.0882

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.182

Gnomad OTH

AF:

0.118

GnomAD3 exomes

AF:

0.127

AC:

31847

AN:

251056

Hom.:

2501

AF XY:

0.131

AC XY:

17718

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.0381

Gnomad AMR exome

AF:

0.0758

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0951

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.162

AC:

237406

AN:

1461864

Hom.:

20823

Cov.:

AF XY:

0.161

AC XY:

116975

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0357

Gnomad4 AMR exome

AF:

0.0780

Gnomad4 ASJ exome

AF:

0.146

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.0977

Gnomad4 FIN exome

AF:

0.165

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.122

AC:

18620

AN:

152186

Hom.:

1471

Cov.:

AF XY:

0.119

AC XY:

8823

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0397

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.146

Gnomad4 EAS

AF:

0.000968

Gnomad4 SAS

AF:

0.0886

Gnomad4 FIN

AF:

0.163

Gnomad4 NFE

AF:

0.182

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.156

Hom.:

2812

Bravo

AF:

0.114

TwinsUK

AF:

0.173

AC:

643

ALSPAC

AF:

0.171

AC:

659

ESP6500AA

AF:

0.0468

AC:

206

ESP6500EA

AF:

0.182

AC:

1567

ExAC

AF:

0.126

AC:

15335

EpiCase

AF:

0.178

EpiControl

AF:

0.171

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 30, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.0010

DANN

Benign

0.52

DEOGEN2

Benign

0.027

Eigen

Benign

-2.8

Eigen_PC

Benign

-2.9

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.20

MetaRNN

Benign

0.00074

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.90

PrimateAI

Benign

0.22

PROVEAN

Benign

0.47

REVEL

Uncertain

0.30

Sift

Benign

0.51

Sift4G

Benign

0.98

Polyphen

0.0

Vest4

0.015

MPC

0.17

ClinPred

0.0073

GERP RS

-11

Varity_R

0.022

gMVP

0.22

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