1-11501880-C-T

Variant names:

• chr1-11501880-C-T
• rs12144924
• NM_020780.2:c.888C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_020780.2(DISP3):​c.888C>T​(p.Val296Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0904 in 1,612,950 control chromosomes in the GnomAD database, including 10,381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.15 (2897 hom., cov: 34)
  • Exomes 𝑓: 0.084 (7484 hom.)
• Consequence: DISP3 NM_020780.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.534

Genes affected

DISP3 (HGNC:29251): (dispatched RND transporter family member 3) Involved in negative regulation of neuron differentiation; positive regulation of lipid metabolic process; and positive regulation of neural precursor cell proliferation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285833 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 1-11501880-C-T is Benign according to our data. Variant chr1-11501880-C-T is described in ClinVar as [Benign]. Clinvar id is 3058907.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.534 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DISP3	NM_020780.2	c.888C>T	p.Val296Val	synonymous_variant	Exon 2 of 21	ENST00000294484.7	NP_065831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DISP3	ENST00000294484.7	c.888C>T	p.Val296Val	synonymous_variant	Exon 2 of 21	1	NM_020780.2	ENSP00000294484.6
ENSG00000285833	ENST00000649975.1	n.137G>A		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23271 AN: 152138 Hom.: 2892 Cov.: 34

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0741

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0449

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0680

Gnomad OTH AF: 0.125

GnomAD3 exomes AF: 0.105 AC: 26001 AN: 248284 Hom.: 2222 AF XY: 0.108 AC XY: 14516 AN XY: 134940

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.0445

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.0384

Gnomad SAS exome AF: 0.203

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.0700

Gnomad OTH exome AF: 0.0813

GnomAD4 exome AF: 0.0839 AC: 122493 AN: 1460694 Hom.: 7484 Cov.: 37 AF XY: 0.0870 AC XY: 63183 AN XY: 726526

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.0477

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.0406

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.0663

Gnomad4 OTH exome AF: 0.0990

GnomAD4 genome AF: 0.153 AC: 23300 AN: 152256 Hom.: 2897 Cov.: 34 AF XY: 0.154 AC XY: 11492 AN XY: 74450

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.0740

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0448

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0680

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0815 Hom.: 1545

Bravo AF: 0.152

Asia WGS AF: 0.146 AC: 508 AN: 3478

EpiCase AF: 0.0727

EpiControl AF: 0.0678

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DISP3-related disorder Benign:1

Oct 30, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs12144924; hg19: chr1-11561937;