NM_018662.3:c.42C>T

Variant names:

• chr1-231626909-C-T
• rs566458514
• NM_018662.3:c.42C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_018662.3(DISC1):​c.42C>T​(p.Gly14Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00058 in 1,502,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00060 (0 hom.)
• Consequence: DISC1 NM_018662.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.715
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-231626909-C-T is Benign according to our data. Variant chr1-231626909-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3049350.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.715 with no splicing effect.

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.42C>T	p.Gly14Gly	synonymous	Exon 1 of 13	NP_061132.2	Q9NRI5-1
	DISC1	NM_001164537.2		c.42C>T	p.Gly14Gly	synonymous	Exon 1 of 14	NP_001158009.1	C4P096
	DISC1	NM_001012957.2		c.42C>T	p.Gly14Gly	synonymous	Exon 1 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.42C>T	p.Gly14Gly	synonymous	Exon 1 of 13	ENSP00000403888.4	Q9NRI5-1
	DISC1	ENST00000366637.8	TSL:5	c.42C>T	p.Gly14Gly	synonymous	Exon 1 of 13	ENSP00000355597.6	Q9NRI5-2
	DISC1	ENST00000366633.7	TSL:1	c.42C>T	p.Gly14Gly	synonymous	Exon 1 of 10	ENSP00000355593.3	Q9NRI5-5

Frequencies

GnomAD3 genomes AF: 0.000396 AC: 60 AN: 151646 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000531

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.000350 AC: 35 AN: 99984 AF XY: 0.000284

Gnomad AFR exome AF: 0.000975

Gnomad AMR exome AF: 0.000320

Gnomad ASJ exome AF: 0.000875

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000199

Gnomad NFE exome AF: 0.000446

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000601 AC: 812 AN: 1350532 Hom.: 0 Cov.: 30 AF XY: 0.000623 AC XY: 415 AN XY: 666578

African (AFR) AF: 0.000109 AC: 3 AN: 27474

American (AMR) AF: 0.000559 AC: 17 AN: 30400

Ashkenazi Jewish (ASJ) AF: 0.000670 AC: 16 AN: 23896

East Asian (EAS) AF: 0.0000304 AC: 1 AN: 32872

South Asian (SAS) AF: 0.00 AC: 0 AN: 76300

European-Finnish (FIN) AF: 0.000121 AC: 4 AN: 33188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4224

European-Non Finnish (NFE) AF: 0.000682 AC: 727 AN: 1066024

Other (OTH) AF: 0.000784 AC: 44 AN: 56154

GnomAD4 genome AF: 0.000395 AC: 60 AN: 151754 Hom.: 0 Cov.: 31 AF XY: 0.000418 AC XY: 31 AN XY: 74170

African (AFR) AF: 0.000193 AC: 8 AN: 41444

American (AMR) AF: 0.000655 AC: 10 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5070

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000531 AC: 36 AN: 67830

Other (OTH) AF: 0.00190 AC: 4 AN: 2104

Alfa AF: 0.000368 Hom.: 0

Bravo AF: 0.000476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DISC1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.0
DANN	Benign	0.89
PhyloP100		-0.71
PromoterAI		-0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.5
Mutation Taster		=299/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs566458514; hg19: chr1-231762655;