1-231626594-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000602956.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSNAX-DISC1	NR_028393.1		n.788+9688G>C		intron	N/A
	TSNAX-DISC1	NR_028394.1		n.916+9688G>C		intron	N/A
	TSNAX-DISC1	NR_028395.1		n.916+9688G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TSNAX-DISC1	ENST00000602956.5	TSL:2	n.495+65339G>C		intron	N/A	ENSP00000473532.1
	TSNAX-DISC1	ENST00000602567.1	TSL:2	n.*197+9688G>C		intron	N/A	ENSP00000473456.1
	TSNAX-DISC1	ENST00000602634.5	TSL:2	n.*213+9688G>C		intron	N/A	ENSP00000473307.1

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

African (AFR) AF: 0.335 AC: 13791 AN: 41138

American (AMR) AF: 0.441 AC: 6718 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1834 AN: 3460

East Asian (EAS) AF: 0.163 AC: 834 AN: 5104

South Asian (SAS) AF: 0.491 AC: 2334 AN: 4752

European-Finnish (FIN) AF: 0.555 AC: 5777 AN: 10400

Middle Eastern (MID) AF: 0.538 AC: 155 AN: 288

European-Non Finnish (NFE) AF: 0.548 AC: 37116 AN: 67742

Other (OTH) AF: 0.471 AC: 983 AN: 2088

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
DANN	Benign	0.64
PhyloP100		0.60
PromoterAI		-0.14	Neutral

Splicing

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

Other links and lift over

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