NM_005999.3:c.496-800G>C

Variant names:

• chr1-231563728-G-C
• rs1655285
• NM_005999.3:c.496-800G>C

Variant summary

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

The NM_005999.3(TSNAX):​c.496-800G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 151,352 control chromosomes in the GnomAD database, including 747 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 (746 hom., cov: 29)
  • Exomes 𝑓: 0.12 (1 hom.)
• Consequence: TSNAX NM_005999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703
• Publications: 9 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005999.3. 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
	TSNAX	NM_005999.3	MANE Select	c.496-800G>C		intron	N/A	NP_005990.1
	TSNAX-DISC1	NR_028393.1		n.525+21117G>C		intron	N/A
	TSNAX-DISC1	NR_028394.1		n.653+2473G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSNAX	ENST00000366639.9	TSL:1 MANE Select	c.496-800G>C		intron	N/A	ENSP00000355599.3
	TSNAX-DISC1	ENST00000602956.5	TSL:2	n.495+2473G>C		intron	N/A	ENSP00000473532.1
	TSNAX	ENST00000475168.1	TSL:2	n.3632+99G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14251 AN: 151140 Hom.: 747 Cov.: 29

Gnomad AFR AF: 0.0728

Gnomad AMI AF: 0.0695

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0837

Gnomad EAS AF: 0.00252

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0734

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0971

GnomAD4 exome AF: 0.122 AC: 12 AN: 98 Hom.: 1 AF XY: 0.111 AC XY: 8 AN XY: 72

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.111 AC: 4 AN: 36

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.130 AC: 7 AN: 54

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.0943 AC: 14256 AN: 151254 Hom.: 746 Cov.: 29 AF XY: 0.0907 AC XY: 6698 AN XY: 73832

African (AFR) AF: 0.0728 AC: 2996 AN: 41158

American (AMR) AF: 0.0748 AC: 1134 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.0837 AC: 290 AN: 3466

East Asian (EAS) AF: 0.00252 AC: 13 AN: 5150

South Asian (SAS) AF: 0.116 AC: 557 AN: 4788

European-Finnish (FIN) AF: 0.0734 AC: 762 AN: 10384

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8211 AN: 67850

Other (OTH) AF: 0.0961 AC: 202 AN: 2102

Alfa AF: 0.0994 Hom.: 113

Bravo AF: 0.0914

Asia WGS AF: 0.0590 AC: 206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.51
DANN	Benign	0.61
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1655285; hg19: chr1-231699474;