Variant rs149444280 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_018662.3(DISC1):c.211G>C(p.Val71Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,758 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DISC1
NM_018662.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.544

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:

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=0.033483118).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3 link	c.211G>C	p.Val71Leu	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.211G>C	p.Val71Leu	missense_variant	Exon 2 of 13	5	NM_018662.3	ENSP00000403888.4	Q9NRI5-1
DISC1	ENST00000366637.8 link	c.211G>C	p.Val71Leu	missense_variant	Exon 2 of 13	5		ENSP00000355597.6	Q9NRI5-2
TSNAX-DISC1	ENST00000602956.5 link	n.*72G>C		non_coding_transcript_exon_variant	Exon 6 of 13	2		ENSP00000473532.1	C4P0D8
TSNAX-DISC1	ENST00000602956.5 link	n.*72G>C		3_prime_UTR_variant	Exon 6 of 13	2		ENSP00000473532.1	C4P0D8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248040

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134364

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461758

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.5

DANN

Benign

0.15

DEOGEN2

Benign

0.0056

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

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.72

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

M_CAP

Benign

0.0057

MetaRNN

Benign

0.033

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

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

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.41

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

REVEL

Benign

0.022

Sift

Benign

0.89

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

Sift4G

Benign

1.0

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

Polyphen

0.0

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

Vest4

0.038

MutPred

0.091

Loss of glycosylation at S72 (P = 0.125);Loss of glycosylation at S72 (P = 0.125);Loss of glycosylation at S72 (P = 0.125);Loss of glycosylation at S72 (P = 0.125);Loss of glycosylation at S72 (P = 0.125);Loss of glycosylation at S72 (P = 0.125);Loss of glycosylation at S72 (P = 0.125);Loss of glycosylation at S72 (P = 0.125);Loss of glycosylation at S72 (P = 0.125);Loss of glycosylation at S72 (P = 0.125);Loss of glycosylation at S72 (P = 0.125);Loss of glycosylation at S72 (P = 0.125);Loss of glycosylation at S72 (P = 0.125);

MVP

0.13

MPC

0.11

ClinPred

0.033

GERP RS

-0.44

Varity_R

0.033

gMVP

0.092

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over