chr1-223005136-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001377229.1(DISP1):​c.3739G>T​(p.Ala1247Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A1247T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

DISP1
NM_001377229.1 missense

Scores

1
18

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0027815998).
BP6
Variant 1-223005136-G-T is Benign according to our data. Variant chr1-223005136-G-T is described in ClinVar as [Benign]. Clinvar id is 1618248.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DISP1NM_001377229.1 linkuse as main transcriptc.3739G>T p.Ala1247Ser missense_variant 9/9 ENST00000675850.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DISP1ENST00000675850.1 linkuse as main transcriptc.3739G>T p.Ala1247Ser missense_variant 9/9 NM_001377229.1 P1

Frequencies

GnomAD3 genomes
AF:
0.000204
AC:
31
AN:
152100
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00779
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000358
AC:
90
AN:
251056
Hom.:
0
AF XY:
0.000354
AC XY:
48
AN XY:
135660
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00695
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000529
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000148
AC:
217
AN:
1461872
Hom.:
0
Cov.:
68
AF XY:
0.000151
AC XY:
110
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00597
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.0000927
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.000431
GnomAD4 genome
AF:
0.000204
AC:
31
AN:
152100
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00779
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000133
Hom.:
2812
ExAC
AF:
0.000239
AC:
29
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 01, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
0.0010
DANN
Benign
0.18
DEOGEN2
Benign
0.024
T
Eigen
Benign
-2.8
Eigen_PC
Benign
-2.9
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.18
T
M_CAP
Benign
0.067
D
MetaRNN
Benign
0.0028
T
MetaSVM
Benign
-0.78
T
MutationAssessor
Benign
-0.69
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.050
N
REVEL
Uncertain
0.33
Sift
Benign
0.67
T
Sift4G
Benign
0.94
T
Polyphen
0.0
B
Vest4
0.098
MutPred
0.16
Gain of glycosylation at A1247 (P = 0.0109);
MVP
0.33
MPC
0.16
ClinPred
0.0040
T
GERP RS
-11
Varity_R
0.037
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.

Other links and lift over

dbSNP: rs9441940; hg19: chr1-223178478; API