chr1-231529288-A-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005999.3(TSNAX):​c.50A>G​(p.Asn17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,614,138 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 33)
Exomes 𝑓: 0.0036 ( 14 hom. )

Consequence

TSNAX
NM_005999.3 missense

Scores

18

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.81

Publications

2 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-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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004289776).
BP6
Variant 1-231529288-A-G is Benign according to our data. Variant chr1-231529288-A-G is described in ClinVar as [Benign]. Clinvar id is 718408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TSNAXNM_005999.3 linkc.50A>G p.Asn17Ser missense_variant Exon 2 of 6 ENST00000366639.9 NP_005990.1 Q99598A0A024R3V8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TSNAXENST00000366639.9 linkc.50A>G p.Asn17Ser missense_variant Exon 2 of 6 1 NM_005999.3 ENSP00000355599.3 Q99598
TSNAX-DISC1ENST00000602956.5 linkn.50A>G non_coding_transcript_exon_variant Exon 2 of 13 2 ENSP00000473532.1 C4P0D8

Frequencies

GnomAD3 genomes
AF:
0.00344
AC:
523
AN:
152196
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000627
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00249
Gnomad ASJ
AF:
0.00461
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.0129
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00426
Gnomad OTH
AF:
0.00478
GnomAD2 exomes
AF:
0.00343
AC:
853
AN:
248690
AF XY:
0.00353
show subpopulations
Gnomad AFR exome
AF:
0.000556
Gnomad AMR exome
AF:
0.00119
Gnomad ASJ exome
AF:
0.00418
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0128
Gnomad NFE exome
AF:
0.00391
Gnomad OTH exome
AF:
0.00409
GnomAD4 exome
AF:
0.00365
AC:
5335
AN:
1461826
Hom.:
14
Cov.:
31
AF XY:
0.00365
AC XY:
2652
AN XY:
727218
show subpopulations
African (AFR)
AF:
0.000627
AC:
21
AN:
33480
American (AMR)
AF:
0.00116
AC:
52
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00436
AC:
114
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00103
AC:
89
AN:
86258
European-Finnish (FIN)
AF:
0.0137
AC:
734
AN:
53388
Middle Eastern (MID)
AF:
0.00104
AC:
6
AN:
5768
European-Non Finnish (NFE)
AF:
0.00373
AC:
4152
AN:
1111980
Other (OTH)
AF:
0.00277
AC:
167
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.444
Heterozygous variant carriers
0
265
530
794
1059
1324
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
150
300
450
600
750
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00343
AC:
522
AN:
152312
Hom.:
2
Cov.:
33
AF XY:
0.00365
AC XY:
272
AN XY:
74484
show subpopulations
African (AFR)
AF:
0.000626
AC:
26
AN:
41560
American (AMR)
AF:
0.00248
AC:
38
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.00461
AC:
16
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5192
South Asian (SAS)
AF:
0.00104
AC:
5
AN:
4828
European-Finnish (FIN)
AF:
0.0129
AC:
137
AN:
10616
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00426
AC:
290
AN:
68024
Other (OTH)
AF:
0.00473
AC:
10
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
22
43
65
86
108
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
10
20
30
40
50
<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:
0.00358
Hom.:
7
Bravo
AF:
0.00248
TwinsUK
AF:
0.00539
AC:
20
ALSPAC
AF:
0.00571
AC:
22
ESP6500AA
AF:
0.00113
AC:
5
ESP6500EA
AF:
0.00430
AC:
37
ExAC
AF:
0.00348
AC:
423
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00327
EpiControl
AF:
0.00284

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Mar 31, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.64
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
15
DANN
Benign
0.96
DEOGEN2
Benign
0.051
T;.
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.67
D
LIST_S2
Benign
0.79
T;T
MetaRNN
Benign
0.0043
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L;.
PhyloP100
2.8
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.61
N;N
REVEL
Benign
0.16
Sift
Benign
0.24
T;T
Sift4G
Benign
0.69
T;T
Polyphen
0.0010
B;.
Vest4
0.13
MVP
0.043
MPC
0.27
ClinPred
0.0046
T
GERP RS
1.8
Varity_R
0.033
gMVP
0.12
Mutation Taster
=96/4
polymorphism

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

Other links and lift over

dbSNP: rs144584692; hg19: chr1-231665034; COSMIC: COSV105279629; COSMIC: COSV105279629; API