NM_005999.3:c.367+5060C>A

Variant names:

• chr1-231547671-C-A
• rs1615409
• NM_005999.3:c.367+5060C>A

Variant summary

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

The NM_005999.3(TSNAX):​c.367+5060C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 150,978 control chromosomes in the GnomAD database, including 19,032 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 0.48 (19032 hom., cov: 30)
• Consequence: TSNAX NM_005999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• Publications: 7 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.701 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.367+5060C>A		intron	N/A	NP_005990.1
	TSNAX-DISC1	NR_028393.1		n.525+5060C>A		intron	N/A
	TSNAX-DISC1	NR_028394.1		n.525+5060C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSNAX	ENST00000366639.9	TSL:1 MANE Select	c.367+5060C>A		intron	N/A	ENSP00000355599.3
	TSNAX-DISC1	ENST00000602956.5	TSL:2	n.367+5060C>A		intron	N/A	ENSP00000473532.1
	TSNAX	ENST00000413309.3	TSL:3	c.388+5060C>A		intron	N/A	ENSP00000397537.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72247 AN: 150858 Hom.: 18974 Cov.: 30

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.479 AC: 72371 AN: 150978 Hom.: 19032 Cov.: 30 AF XY: 0.473 AC XY: 34867 AN XY: 73722

African (AFR) AF: 0.708 AC: 29250 AN: 41300

American (AMR) AF: 0.498 AC: 7568 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1158 AN: 3452

East Asian (EAS) AF: 0.538 AC: 2731 AN: 5076

South Asian (SAS) AF: 0.433 AC: 2066 AN: 4766

European-Finnish (FIN) AF: 0.285 AC: 2963 AN: 10394

Middle Eastern (MID) AF: 0.376 AC: 109 AN: 290

European-Non Finnish (NFE) AF: 0.372 AC: 25120 AN: 67502

Other (OTH) AF: 0.464 AC: 973 AN: 2096

Alfa AF: 0.416 Hom.: 1717

Bravo AF: 0.507

Asia WGS AF: 0.498 AC: 1732 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.080
DANN	Benign	0.35
PhyloP100		-2.4
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: rs1615409; hg19: chr1-231683417; COSMIC: COSV64146048; COSMIC: COSV64146048;