Genetic Variant TSNAX:c.496-800G>C (chr1-231563728-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.703

Publications

9 publications found

Variant links:

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 links:

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]

TSNAX-DISC1 links:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TSNAX	NM_005999.3	MANE Select	c.496-800G>C	intron	N/A	NP_005990.1	Q99598
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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TSNAX	ENST00000366639.9	TSL:1 MANE Select	c.496-800G>C	intron	N/A	ENSP00000355599.3	Q99598
TSNAX-DISC1	ENST00000602956.5	TSL:2	n.495+2473G>C	intron	N/A	ENSP00000473532.1	C4P0D8
TSNAX	ENST00000947977.1		c.541-800G>C	intron	N/A	ENSP00000618036.1

Frequencies

GnomAD3 genomes

AF:

0.0943

AC:

14251

AN:

151140

Hom.:

747

Cov.:

show subpopulations

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:

AN:

Hom.:

AF XY:

0.111

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.111

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.130

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0943

AC:

14256

AN:

151254

Hom.:

746

Cov.:

AF XY:

0.0907

AC XY:

6698

AN XY:

73832

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.121

AC:

8211

AN:

67850

Other (OTH)

AF:

0.0961

AC:

202

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

624

1248

1872

2496

3120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.61

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over