1-11502856-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_020780.2(DISP3):c.1275C>T(p.Phe425=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 1,614,002 control chromosomes in the GnomAD database, including 8,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1765 hom., cov: 33)
  • Exomes 𝑓: 0.081 (6490 hom.)
• Consequence: DISP3 NM_020780.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.384

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 1-11502856-C-T is Benign according to our data. Variant chr1-11502856-C-T is described in ClinVar as [Benign]. Clinvar id is 3060865.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.384 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISP3	NM_020780.2	c.1275C>T	p.Phe425=	synonymous_variant	3/21	ENST00000294484.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISP3	ENST00000294484.7	c.1275C>T	p.Phe425=	synonymous_variant	3/21	1	NM_020780.2	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19334 AN: 152124 Hom.: 1757 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.0456

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.0677

Gnomad OTH AF: 0.111

GnomAD3 exomes AF: 0.0984 AC: 24537 AN: 249370 Hom.: 1781 AF XY: 0.103 AC XY: 13926 AN XY: 135304

Gnomad AFR exome AF: 0.259

Gnomad AMR exome AF: 0.0401

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.0384

Gnomad SAS exome AF: 0.204

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.0700

Gnomad OTH exome AF: 0.0784

GnomAD4 exome AF: 0.0814 AC: 119008 AN: 1461760 Hom.: 6490 Cov.: 32 AF XY: 0.0849 AC XY: 61714 AN XY: 727176

Gnomad4 AFR exome AF: 0.262

Gnomad4 AMR exome AF: 0.0433

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.0406

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.0662

Gnomad4 OTH exome AF: 0.0941

GnomAD4 genome AF: 0.127 AC: 19362 AN: 152242 Hom.: 1765 Cov.: 33 AF XY: 0.130 AC XY: 9687 AN XY: 74444

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.0659

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.0455

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0677

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0966 Hom.: 584

Bravo AF: 0.123

Asia WGS AF: 0.141 AC: 491 AN: 3478

EpiCase AF: 0.0723

EpiControl AF: 0.0675

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

DISP3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

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	-0.27
Cadd	Benign	10
Dann	Benign	0.72

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: rs60362998; hg19: chr1-11562913; COSMIC: COSV53833270;