1-231528457-G-C

Variant names:

• chr1-231528457-G-C
• rs1630250
• ENST00000662216.1:c.-323C>G

Variant summary

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

The ENST00000662216.1(ENSG00000287856):​c.-323C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 450,060 control chromosomes in the GnomAD database, including 43,466 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 (19308 hom., cov: 33)
  • Exomes 𝑓: 0.39 (24158 hom.)
• Consequence: ENSG00000287856 ENST00000662216.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60
• Publications: 12 publications found

Genes affected

ENSG00000287856 (HGNC:):

ENSG00000233461 (HGNC:40594):

TSNAX-DT (HGNC:58098):

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TSNAX	NM_005999.3	c.-354G>C		upstream_gene_variant		ENST00000366639.9	NP_005990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000287856	ENST00000662216.1	c.-323C>G		5_prime_UTR_variant	Exon 1 of 7			ENSP00000499467.1
TSNAX	ENST00000366639.9	c.-354G>C		upstream_gene_variant		1	NM_005999.3	ENSP00000355599.3
TSNAX-DISC1	ENST00000602956.5	n.-354G>C		upstream_gene_variant		2		ENSP00000473532.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72760 AN: 152026 Hom.: 19253 Cov.: 33

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.392 AC: 116743 AN: 297916 Hom.: 24158 Cov.: 0 AF XY: 0.392 AC XY: 60138 AN XY: 153574

African (AFR) AF: 0.708 AC: 5570 AN: 7862

American (AMR) AF: 0.516 AC: 4682 AN: 9082

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 3554 AN: 10124

East Asian (EAS) AF: 0.553 AC: 13321 AN: 24076

South Asian (SAS) AF: 0.412 AC: 6379 AN: 15474

European-Finnish (FIN) AF: 0.300 AC: 7236 AN: 24122

Middle Eastern (MID) AF: 0.353 AC: 502 AN: 1422

European-Non Finnish (NFE) AF: 0.363 AC: 67728 AN: 186820

Other (OTH) AF: 0.410 AC: 7771 AN: 18934

GnomAD4 genome AF: 0.479 AC: 72880 AN: 152144 Hom.: 19308 Cov.: 33 AF XY: 0.472 AC XY: 35141 AN XY: 74374

African (AFR) AF: 0.714 AC: 29657 AN: 41522

American (AMR) AF: 0.497 AC: 7605 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1153 AN: 3470

East Asian (EAS) AF: 0.532 AC: 2738 AN: 5142

South Asian (SAS) AF: 0.427 AC: 2060 AN: 4824

European-Finnish (FIN) AF: 0.283 AC: 3000 AN: 10590

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25145 AN: 67982

Other (OTH) AF: 0.463 AC: 978 AN: 2114

Alfa AF: 0.251 Hom.: 534

Bravo AF: 0.508

Asia WGS AF: 0.500 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.58
PhyloP100		-2.6
PromoterAI		0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1630250; hg19: chr1-231664203;