rs144584692

Variant names:

• chr1-231529288-A-G
• rs144584692
• NM_005999.3:c.50A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.81
• Publications: 2 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 -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 VariationId is 718408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSNAX	NM_005999.3	MANE Select	c.50A>G	p.Asn17Ser	missense	Exon 2 of 6	NP_005990.1	Q99598
	TSNAX-DISC1	NR_028393.1		n.208A>G		non_coding_transcript_exon	Exon 2 of 16
	TSNAX-DISC1	NR_028394.1		n.208A>G		non_coding_transcript_exon	Exon 2 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSNAX	ENST00000366639.9	TSL:1 MANE Select	c.50A>G	p.Asn17Ser	missense	Exon 2 of 6	ENSP00000355599.3	Q99598
	TSNAX-DISC1	ENST00000602956.5	TSL:2	n.50A>G		non_coding_transcript_exon	Exon 2 of 13	ENSP00000473532.1	C4P0D8
	TSNAX	ENST00000947977.1		c.95A>G	p.Asn32Ser	missense	Exon 2 of 6	ENSP00000618036.1

Frequencies

GnomAD3 genomes AF: 0.00344 AC: 523 AN: 152196 Hom.: 2 Cov.: 33

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

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

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

GnomAD4 genome AF: 0.00343 AC: 522 AN: 152312 Hom.: 2 Cov.: 33 AF XY: 0.00365 AC XY: 272 AN XY: 74484

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

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.8
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.16
Sift	Benign	0.24	T
Sift4G	Benign	0.69	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

Other links and lift over

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