1-232038427-T-C

Variant names:

• chr1-232038427-T-C
• rs9729179
• NM_018662.3:c.*1596T>C

Variant summary

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

The NM_018662.3(DISC1):​c.*1596T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,910 control chromosomes in the GnomAD database, including 10,455 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 0.36 (10454 hom., cov: 31)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: DISC1 NM_018662.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISC1	NM_018662.3	c.*1596T>C		3_prime_UTR_variant	Exon 13 of 13	ENST00000439617.8	NP_061132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISC1	ENST00000439617.8	c.*1596T>C		3_prime_UTR_variant	Exon 13 of 13	5	NM_018662.3	ENSP00000403888.4
DISC1	ENST00000366637.8	c.*1596T>C		3_prime_UTR_variant	Exon 13 of 13	5		ENSP00000355597.6
DISC1	ENST00000622252.4	c.*2702T>C		3_prime_UTR_variant	Exon 12 of 12	5		ENSP00000481791.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53903 AN: 151788 Hom.: 10442 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

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) AF: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.355 AC: 53964 AN: 151906 Hom.: 10454 Cov.: 31 AF XY: 0.351 AC XY: 26050 AN XY: 74252

African (AFR) AF: 0.510 AC: 21120 AN: 41398

American (AMR) AF: 0.312 AC: 4757 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3468

East Asian (EAS) AF: 0.334 AC: 1721 AN: 5152

South Asian (SAS) AF: 0.261 AC: 1259 AN: 4818

European-Finnish (FIN) AF: 0.302 AC: 3190 AN: 10550

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19727 AN: 67942

Other (OTH) AF: 0.343 AC: 724 AN: 2110

Alfa AF: 0.309 Hom.: 29129

Bravo AF: 0.367

Asia WGS AF: 0.337 AC: 1172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.039
DANN	Benign	0.51
PhyloP100		-1.4
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: rs9729179; hg19: chr1-232174173;