chr1-231818681-C-G

Variant names:

• chr1-231818681-C-G
• rs1535530
• ENST00000602956.5:n.*2006C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.708
• Publications: 10 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:):

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]

ACMG classification

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000602956.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	NM_018662.3	MANE Select	c.1981+164C>G		intron	N/A	NP_061132.2
	TSNAX-DISC1	NR_028394.1		n.2994C>G		non_coding_transcript_exon	Exon 14 of 14
	TSNAX-DISC1	NR_028395.1		n.2891C>G		non_coding_transcript_exon	Exon 13 of 13

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSNAX-DISC1	ENST00000602956.5	TSL:2	n.*2006C>G		non_coding_transcript_exon	Exon 13 of 13	ENSP00000473532.1
	DISC1	ENST00000602281.5	TSL:1	c.*156C>G		3_prime_UTR	Exon 9 of 9	ENSP00000473425.1
	DISC1	ENST00000539444.5	TSL:1	c.*302C>G		3_prime_UTR	Exon 8 of 8	ENSP00000440953.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000545 AC: 7 AN: 1285528 Hom.: 0 Cov.: 41 AF XY: 0.00000482 AC XY: 3 AN XY: 622920

African (AFR) AF: 0.00 AC: 0 AN: 28234

American (AMR) AF: 0.00 AC: 0 AN: 19822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18950

East Asian (EAS) AF: 0.00 AC: 0 AN: 34714

South Asian (SAS) AF: 0.00 AC: 0 AN: 60306

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5054

European-Non Finnish (NFE) AF: 0.00000679 AC: 7 AN: 1031002

Other (OTH) AF: 0.00 AC: 0 AN: 53494

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 92697

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
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

Other links and lift over

dbSNP: rs1535530; hg19: chr1-231954427;