rs2072994

chr1-11519413-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020780.2(DISP3):c.1948G>A(p.Ala650Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,613,438 control chromosomes in the GnomAD database, including 287,725 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.47 (20740 hom., cov: 32)
  • Exomes 𝑓: 0.59 (266985 hom.)
• Consequence: DISP3 NM_020780.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.522

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.6140498E-6).
• BP6: Variant 1-11519413-G-A is Benign according to our data. Variant chr1-11519413-G-A is described in ClinVar as [Benign]. Clinvar id is 3060671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISP3	NM_020780.2	c.1948G>A	p.Ala650Thr	missense_variant	8/21	ENST00000294484.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISP3	ENST00000294484.7	c.1948G>A	p.Ala650Thr	missense_variant	8/21	1	NM_020780.2	P1

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71608 AN: 151894 Hom.: 20735 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.484

GnomAD3 exomes AF: 0.555 AC: 138471 AN: 249316 Hom.: 42314 AF XY: 0.552 AC XY: 74741 AN XY: 135280

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.725

Gnomad ASJ exome AF: 0.537

Gnomad EAS exome AF: 0.268

Gnomad SAS exome AF: 0.407

Gnomad FIN exome AF: 0.642

Gnomad NFE exome AF: 0.632

Gnomad OTH exome AF: 0.598

GnomAD4 exome AF: 0.593 AC: 866949 AN: 1461426 Hom.: 266985 Cov.: 68 AF XY: 0.588 AC XY: 427632 AN XY: 727030

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.715

Gnomad4 ASJ exome AF: 0.539

Gnomad4 EAS exome AF: 0.256

Gnomad4 SAS exome AF: 0.410

Gnomad4 FIN exome AF: 0.646

Gnomad4 NFE exome AF: 0.630

Gnomad4 OTH exome AF: 0.556

GnomAD4 genome AF: 0.471 AC: 71624 AN: 152012 Hom.: 20740 Cov.: 32 AF XY: 0.470 AC XY: 34917 AN XY: 74304

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.483

Alfa AF: 0.585 Hom.: 33295

Bravo AF: 0.461

TwinsUK AF: 0.628 AC: 2327

ALSPAC AF: 0.605 AC: 2330

ESP6500AA AF: 0.140 AC: 566

ESP6500EA AF: 0.616 AC: 5141

ExAC AF: 0.543 AC: 65682

Asia WGS AF: 0.307 AC: 1067 AN: 3478

EpiCase AF: 0.612

EpiControl AF: 0.618

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 16, 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
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	0.11
Dann	Benign	0.24
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0000036	T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.12
Sift	Benign	0.66	T
Sift4G	Benign	0.83	T
Polyphen		0.0040	B
Vest4		0.0090
MPC		0.36
ClinPred		0.0052	T
GERP RS		-5.8
Varity_R		0.028
gMVP		0.32

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: rs2072994; hg19: chr1-11579470; COSMIC: COSV53820610;