rs3738401

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018662.3(DISC1):c.791G>A(p.Arg264Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,613,978 control chromosomes in the GnomAD database, including 77,384 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 not provided (no stars).

Frequency

Genomes: 𝑓 0.26 ( 5671 hom., cov: 33)

Exomes 𝑓: 0.31 ( 71713 hom. )

Consequence

DISC1
NM_018662.3 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -1.13

Variant links:

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]

DISC1 links:

TSNAX-DISC1 (HGNC:49177): (TSNAX-DISC1 readthrough (NMD candidate)) This gene represents naturally occurring read-through transcription between the neighboring TSNAX (translin-associated factor X) and DISC1 (disrupted in schizophrenia 1) genes on chromosome 1. Alternative splicing results in multiple transcript variants, all of which are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to be protein-coding. These alterations in gene processing may be associated with risk for psychiatric illness, most notably, schizophrenia. [provided by RefSeq, Nov 2010]

TSNAX-DISC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018889904).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3 link	c.791G>A	p.Arg264Gln	missense_variant	Exon 2 of 13	ENST00000439617.8	NP_061132.2	Q9NRI5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DISC1	ENST00000439617.8 link	c.791G>A	p.Arg264Gln	missense_variant	Exon 2 of 13	5	NM_018662.3	ENSP00000403888.4	Q9NRI5-1
DISC1	ENST00000366637.8 link	c.791G>A	p.Arg264Gln	missense_variant	Exon 2 of 13	5		ENSP00000355597.6	Q9NRI5-2
TSNAX-DISC1	ENST00000602956.5 link	n.*652G>A		non_coding_transcript_exon_variant	Exon 6 of 13	2		ENSP00000473532.1	C4P0D8
TSNAX-DISC1	ENST00000602956.5 link	n.*652G>A		3_prime_UTR_variant	Exon 6 of 13	2		ENSP00000473532.1	C4P0D8

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39622

AN:

152140

Hom.:

5672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.178

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.303

GnomAD3 exomes

AF:

0.296

AC:

73630

AN:

248600

Hom.:

11388

AF XY:

0.295

AC XY:

39771

AN XY:

134622

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.362

Gnomad ASJ exome

AF:

0.304

Gnomad EAS exome

AF:

0.244

Gnomad SAS exome

AF:

0.263

Gnomad FIN exome

AF:

0.287

Gnomad NFE exome

AF:

0.317

Gnomad OTH exome

AF:

0.318

GnomAD4 exome

AF:

0.311

AC:

454502

AN:

1461716

Hom.:

71713

Cov.:

AF XY:

0.309

AC XY:

225018

AN XY:

727142

show subpopulations

Gnomad4 AFR exome

AF:

0.135

Gnomad4 AMR exome

AF:

0.355

Gnomad4 ASJ exome

AF:

0.306

Gnomad4 EAS exome

AF:

0.250

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.290

Gnomad4 NFE exome

AF:

0.322

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.260

AC:

39633

AN:

152262

Hom.:

5671

Cov.:

AF XY:

0.257

AC XY:

19116

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.140

Gnomad4 AMR

AF:

0.316

Gnomad4 ASJ

AF:

0.289

Gnomad4 EAS

AF:

0.237

Gnomad4 SAS

AF:

0.240

Gnomad4 FIN

AF:

0.283

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.304

Alfa

AF:

0.301

Hom.:

14455

Bravo

AF:

0.260

TwinsUK

AF:

0.320

AC:

1187

ALSPAC

AF:

0.311

AC:

1199

ESP6500AA

AF:

0.147

AC:

648

ESP6500EA

AF:

0.318

AC:

2734

ExAC

AF:

0.292

AC:

35430

Asia WGS

AF:

0.233

AC:

814

AN:

3478

EpiCase

AF:

0.316

EpiControl

AF:

0.319

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

Psychiatry Genetics Yale University

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.051

DANN

Benign

0.82

DEOGEN2

Benign

0.0097

.;.;.;.;.;.;.;.;.;T;.;T;.

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0072

LIST_S2

Benign

0.52

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.86

N;N;N;N;.;N;N;N;N;.;.;N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.11

N;N;.;N;N;N;.;N;N;.;.;N;.

REVEL

Benign

0.028

Sift

Benign

0.39

T;T;.;.;T;T;.;T;T;.;.;T;.

Sift4G

Benign

0.43

T;T;T;T;T;T;T;T;T;T;T;T;.

Polyphen

0.0010

B;.;.;.;B;B;.;.;B;.;.;B;.

Vest4

0.010

MPC

0.13

ClinPred

0.016

GERP RS

-9.9

Varity_R

0.021

gMVP

0.060

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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