chr1-231557942-G-T

Variant names:

• chr1-231557942-G-T
• rs766288
• NM_005999.3:c.368-3186G>T

Variant summary

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

The NM_005999.3(TSNAX):​c.368-3186G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,900 control chromosomes in the GnomAD database, including 12,647 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 0.40 (12647 hom., cov: 32)
• Consequence: TSNAX NM_005999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 19 publications found

Genes affected

TSNAX (HGNC:12380): (translin associated factor X) This gene encodes a protein which specifically interacts with translin, a DNA-binding protein that binds consensus sequences at breakpoint junctions of chromosomal translocations. The encoded protein contains bipartite nuclear targeting sequences that may provide nuclear transport for translin, which lacks any nuclear targeting motifs. [provided by RefSeq, Jul 2008]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSNAX	NM_005999.3	c.368-3186G>T		intron_variant	Intron 4 of 5	ENST00000366639.9	NP_005990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSNAX	ENST00000366639.9	c.368-3186G>T		intron_variant	Intron 4 of 5	1	NM_005999.3	ENSP00000355599.3
TSNAX-DISC1	ENST00000602956.5	n.368-3186G>T		intron_variant	Intron 4 of 12	2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60831 AN: 151782 Hom.: 12618 Cov.: 32

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.395

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.401 AC: 60912 AN: 151900 Hom.: 12647 Cov.: 32 AF XY: 0.393 AC XY: 29197 AN XY: 74242

African (AFR) AF: 0.501 AC: 20693 AN: 41334

American (AMR) AF: 0.465 AC: 7103 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1097 AN: 3470

East Asian (EAS) AF: 0.322 AC: 1666 AN: 5172

South Asian (SAS) AF: 0.327 AC: 1574 AN: 4814

European-Finnish (FIN) AF: 0.266 AC: 2816 AN: 10582

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24595 AN: 67942

Other (OTH) AF: 0.396 AC: 835 AN: 2108

Alfa AF: 0.381 Hom.: 2285

Bravo AF: 0.424

Asia WGS AF: 0.340 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.72
PhyloP100		0.072
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: rs766288; hg19: chr1-231693688;