chr1-231694266-C-T
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_018662.3(DISC1):c.508C>T(p.Arg170Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000416 in 1,614,250 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00047 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00041 ( 5 hom. )
Consequence
DISC1
NM_018662.3 missense
NM_018662.3 missense
Scores
4
13
Clinical Significance
Conservation
PhyloP100: 0.200
Genes affected
DISC1 (HGNC:2888): (DISC1 scaffold protein) This gene encodes a protein with multiple coiled coil motifs which is located in the nucleus, cytoplasm and mitochondria. The protein is involved in neurite outgrowth and cortical development through its interaction with other proteins. This gene is disrupted in a t(1;11)(q42.1;q14.3) translocation which segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
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=0.0037977397).
BP6
?
Variant 1-231694266-C-T is Benign according to our data. Variant chr1-231694266-C-T is described in ClinVar as [Benign]. Clinvar id is 783018.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAdExome at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DISC1 | NM_018662.3 | c.508C>T | p.Arg170Cys | missense_variant | 2/13 | ENST00000439617.8 | |
TSNAX-DISC1 | NR_028393.1 | n.1229C>T | non_coding_transcript_exon_variant | 6/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DISC1 | ENST00000439617.8 | c.508C>T | p.Arg170Cys | missense_variant | 2/13 | 5 | NM_018662.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000473 AC: 72AN: 152262Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
72
AN:
152262
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00190 AC: 472AN: 248748Hom.: 4 AF XY: 0.00126 AC XY: 170AN XY: 134706
GnomAD3 exomes
AF:
AC:
472
AN:
248748
Hom.:
AF XY:
AC XY:
170
AN XY:
134706
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000410 AC: 600AN: 1461870Hom.: 5 Cov.: 32 AF XY: 0.000329 AC XY: 239AN XY: 727232
GnomAD4 exome
AF:
AC:
600
AN:
1461870
Hom.:
Cov.:
32
AF XY:
AC XY:
239
AN XY:
727232
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000473 AC: 72AN: 152380Hom.: 0 Cov.: 33 AF XY: 0.000403 AC XY: 30AN XY: 74524
GnomAD4 genome
?
AF:
AC:
72
AN:
152380
Hom.:
Cov.:
33
AF XY:
AC XY:
30
AN XY:
74524
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
157
Asia WGS
AF:
AC:
2
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
DISC1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 16, 2022 | 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N;.;N;N;N;N;.;.;N;N
MutationTaster
Benign
N;N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;N;.;N;N;N;.;N;N;.;.;N;.
REVEL
Benign
Sift
Uncertain
D;D;.;.;D;D;.;D;D;.;.;D;.
Sift4G
Benign
T;T;T;D;T;T;T;T;T;T;T;T;.
Polyphen
P;.;.;.;D;D;.;.;D;.;.;D;.
Vest4
MVP
MPC
0.46
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at