1-231626594-G-C

Variant names:

• chr1-231626594-G-C
• rs3738398
• ENST00000602956.5:n.495+65339G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000602956.5(TSNAX-DISC1):​n.495+65339G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,112 control chromosomes in the GnomAD database, including 17,226 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 0.46 (17226 hom., cov: 27)
• Consequence: TSNAX-DISC1 ENST00000602956.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599

Genes affected

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]

DISC1 (HGNC:2888): (DISC1 scaffold protein) This gene encodes a protein with multiple coiled coil motifs which is located in the nucleus, cytoplasm and mitochondria. The protein is involved in neurite outgrowth and cortical development through its interaction with other proteins. This gene is disrupted in a t(1;11)(q42.1;q14.3) translocation which segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.-274G>C		upstream_gene_variant		ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TSNAX-DISC1	ENST00000602956.5	n.495+65339G>C		intron_variant	Intron 5 of 12	2		ENSP00000473532.1
DISC1	ENST00000439617.8	c.-274G>C		upstream_gene_variant		5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.-274G>C		upstream_gene_variant		5		ENSP00000355597.6

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70142 AN: 150990 Hom.: 17227 Cov.: 27

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.542

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.475

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.464 AC: 70151 AN: 151112 Hom.: 17226 Cov.: 27 AF XY: 0.464 AC XY: 34274 AN XY: 73806

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.530

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.471

Alfa AF: 0.396 Hom.: 1198

Bravo AF: 0.448

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3738398; hg19: chr1-231762340; COSMIC: COSV54403256;