Genetic Variant ENSG00000287856:c.-323C>G (chr1-231528457-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.60

Variant links:

Genes affected

ENSG00000287856 (HGNC:):

ENSG00000287856 links:

ENSG00000233461 (HGNC:58098):

ENSG00000233461 links:

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 made for transcript

Verdict is Benign. Variant got -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 link	c.-354G>C		upstream_gene_variant		ENST00000366639.9	NP_005990.1	Q99598A0A024R3V8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000287856	ENST00000662216.1 link	c.-323C>G	5_prime_UTR_variant	Exon 1 of 7			ENSP00000499467.1	A0A590UJK7
TSNAX	ENST00000366639.9 link	c.-354G>C	upstream_gene_variant		1	NM_005999.3	ENSP00000355599.3	Q99598
TSNAX-DISC1	ENST00000602956.5 link	n.-354G>C	upstream_gene_variant		2		ENSP00000473532.1	C4P0D8

Frequencies

GnomAD3 genomes

AF:

0.479

AC:

72760

AN:

152026

Hom.:

19253

Cov.:

show subpopulations

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.:

AF XY:

0.392

AC XY:

60138

AN XY:

153574

show subpopulations

Gnomad4 AFR exome

AF:

0.708

Gnomad4 AMR exome

AF:

0.516

Gnomad4 ASJ exome

AF:

0.351

Gnomad4 EAS exome

AF:

0.553

Gnomad4 SAS exome

AF:

0.412

Gnomad4 FIN exome

AF:

0.300

Gnomad4 NFE exome

AF:

0.363

Gnomad4 OTH exome

AF:

0.410

GnomAD4 genome

AF:

0.479

AC:

72880

AN:

152144

Hom.:

19308

Cov.:

AF XY:

0.472

AC XY:

35141

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.714

Gnomad4 AMR

AF:

0.497

Gnomad4 ASJ

AF:

0.332

Gnomad4 EAS

AF:

0.532

Gnomad4 SAS

AF:

0.427

Gnomad4 FIN

AF:

0.283

Gnomad4 NFE

AF:

0.370

Gnomad4 OTH

AF:

0.463

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over