rs2295959

Variant names:

• chr1-231818936-C-T
• rs2295959
• ENST00000602956.5:n.*2261C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000602956.5(TSNAX-DISC1):​n.*2261C>T 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 0.0612 in 1,009,826 control chromosomes in the GnomAD database, including 2,685 homozygotes. 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: 𝑓 0.094 (967 hom., cov: 32)
  • Exomes 𝑓: 0.055 (1718 hom.)
• Consequence: TSNAX-DISC1 ENST00000602956.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487
• Publications: 11 publications found

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]

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]

ENSG00000286071 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.1981+419C>T		intron_variant	Intron 9 of 12	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSNAX-DISC1	ENST00000602956.5	n.*2261C>T		non_coding_transcript_exon_variant	Exon 13 of 13	2		ENSP00000473532.1
TSNAX-DISC1	ENST00000602956.5	n.*2261C>T		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000473532.1
DISC1	ENST00000439617.8	c.1981+419C>T		intron_variant	Intron 9 of 12	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.1981+419C>T		intron_variant	Intron 9 of 12	5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.0937 AC: 14247 AN: 152108 Hom.: 963 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0527

Gnomad OTH AF: 0.0912

GnomAD4 exome AF: 0.0554 AC: 47533 AN: 857600 Hom.: 1718 Cov.: 33 AF XY: 0.0550 AC XY: 21852 AN XY: 397248

African (AFR) AF: 0.139 AC: 2243 AN: 16102

American (AMR) AF: 0.104 AC: 355 AN: 3400

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 560 AN: 5566

East Asian (EAS) AF: 0.340 AC: 1605 AN: 4716

South Asian (SAS) AF: 0.123 AC: 2333 AN: 19010

European-Finnish (FIN) AF: 0.0277 AC: 37 AN: 1334

Middle Eastern (MID) AF: 0.0972 AC: 165 AN: 1698

European-Non Finnish (NFE) AF: 0.0488 AC: 37939 AN: 777114

Other (OTH) AF: 0.0801 AC: 2296 AN: 28660

GnomAD4 genome AF: 0.0937 AC: 14271 AN: 152226 Hom.: 967 Cov.: 32 AF XY: 0.0953 AC XY: 7091 AN XY: 74426

African (AFR) AF: 0.130 AC: 5400 AN: 41538

American (AMR) AF: 0.115 AC: 1760 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 370 AN: 3472

East Asian (EAS) AF: 0.352 AC: 1819 AN: 5162

South Asian (SAS) AF: 0.128 AC: 619 AN: 4818

European-Finnish (FIN) AF: 0.0427 AC: 453 AN: 10608

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0527 AC: 3586 AN: 68016

Other (OTH) AF: 0.0936 AC: 198 AN: 2116

Alfa AF: 0.0659 Hom.: 723

Bravo AF: 0.101

Asia WGS AF: 0.236 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.82
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2295959; hg19: chr1-231954682;