dbSNP rs756999364: TSNAX:p.Ile137Val (chr1-231561169-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005999.3(TSNAX):c.409A>G(p.Ile137Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,459,008 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I137F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TSNAX
NM_005999.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.33

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSNAX	NM_005999.3 link	c.409A>G	p.Ile137Val	missense_variant	Exon 5 of 6	ENST00000366639.9	NP_005990.1	Q99598A0A024R3V8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSNAX	ENST00000366639.9 link	c.409A>G	p.Ile137Val	missense_variant	Exon 5 of 6	1	NM_005999.3	ENSP00000355599.3		Q99598
TSNAX-DISC1	ENST00000602956.5 link	n.409A>G		non_coding_transcript_exon_variant	Exon 5 of 13	2		ENSP00000473532.1		C4P0D8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1459008

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

725690

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33336

American (AMR)

AF:

0.00

AC:

AN:

44410

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39524

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85450

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1110720

Other (OTH)

AF:

0.00

AC:

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

T;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.0063

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.2

M;.

PhyloP100

8.3

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.72

N;N

REVEL

Benign

0.17

Sift

Benign

0.056

T;D

Sift4G

Benign

0.079

T;T

Polyphen

0.64

P;.

Vest4

0.62

MutPred

0.65

Loss of catalytic residue at L142 (P = 0.0249);.;

MVP

0.33

MPC

0.35

ClinPred

0.92

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.45

Mutation Taster

=42/58

disease causing

(source)

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

Publications

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rs756999364

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over