rs16856322

Variant names:

• chr1-232041241-C-T
• rs16856322
• NM_018662.3:c.*4410C>T

Variant summary

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

The NM_018662.3(DISC1):​c.*4410C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,962 control chromosomes in the GnomAD database, including 6,712 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 0.29 (6712 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DISC1 NM_018662.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0180
• Publications: 11 publications found

Genes affected

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]

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018662.3. 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
	DISC1	NM_018662.3	MANE Select	c.*4410C>T		3_prime_UTR	Exon 13 of 13	NP_061132.2	Q9NRI5-1
	DISC1	NM_001164537.2		c.*4410C>T		3_prime_UTR	Exon 14 of 14	NP_001158009.1	C4P096
	DISC1	NM_001012957.2		c.*4410C>T		3_prime_UTR	Exon 13 of 13	NP_001012975.1	Q9NRI5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DISC1	ENST00000439617.8	TSL:5 MANE Select	c.*4410C>T		3_prime_UTR	Exon 13 of 13	ENSP00000403888.4	Q9NRI5-1
	DISC1	ENST00000622252.4	TSL:5	c.*5516C>T		3_prime_UTR	Exon 12 of 12	ENSP00000481791.1	C4P0A0
	DISC1	ENST00000366637.8	TSL:5	c.*4410C>T		downstream_gene	N/A	ENSP00000355597.6	Q9NRI5-2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44647 AN: 151844 Hom.: 6711 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.295

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.294 AC: 44682 AN: 151962 Hom.: 6712 Cov.: 32 AF XY: 0.292 AC XY: 21699 AN XY: 74276

African (AFR) AF: 0.313 AC: 12954 AN: 41418

American (AMR) AF: 0.285 AC: 4343 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 919 AN: 3470

East Asian (EAS) AF: 0.333 AC: 1722 AN: 5170

South Asian (SAS) AF: 0.259 AC: 1248 AN: 4820

European-Finnish (FIN) AF: 0.291 AC: 3070 AN: 10560

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19308 AN: 67946

Other (OTH) AF: 0.294 AC: 621 AN: 2110

Alfa AF: 0.290 Hom.: 8312

Bravo AF: 0.296

Asia WGS AF: 0.320 AC: 1113 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.4
DANN	Benign	0.85
PhyloP100		0.018
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16856322; hg19: chr1-232176987;