Genetic Variant TSNAX-DISC1:n.*2006C>G (chr1-231818681-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000602956.5(TSNAX-DISC1):n.*2006C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000545 in 1,285,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000054 ( 0 hom. )

Consequence

TSNAX-DISC1
ENST00000602956.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.708

Publications

10 publications found

Variant links:

Genes affected

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:

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:

ENSG00000286071 (HGNC:):

ENSG00000286071 links:

DISC2 (HGNC:2889): (disrupted in schizophrenia 2) DISC2 is thought to specify a noncoding RNA molecule antisense to DISC1 (MIM 605210). Both genes were found to be disrupted by a translocation in a large schizophrenia (MIM 181500) kindred.[supplied by OMIM, Jul 2002]

DISC2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3 link	c.1981+164C>G		intron_variant	Intron 9 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
TSNAX-DISC1	ENST00000602956.5 link	n.*2006C>G	non_coding_transcript_exon_variant	Exon 13 of 13	2		ENSP00000473532.1
TSNAX-DISC1	ENST00000602956.5 link	n.*2006C>G	3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000473532.1
DISC1	ENST00000439617.8 link	c.1981+164C>G	intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8 link	c.1981+164C>G	intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000545

AC:

AN:

1285528

Hom.:

Cov.:

AF XY:

0.00000482

AC XY:

AN XY:

622920

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28234

American (AMR)

AF:

0.00

AC:

AN:

19822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18950

East Asian (EAS)

AF:

0.00

AC:

AN:

34714

South Asian (SAS)

AF:

0.00

AC:

AN:

60306

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33952

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5054

European-Non Finnish (NFE)

AF:

0.00000679

AC:

AN:

1031002

Other (OTH)

AF:

0.00

AC:

AN:

53494

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

92697

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.9

(source)

DANN

Benign

0.71

PhyloP100

-0.71

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over