1-11519447-G-C

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.1982G>C(p.Gly661Ala) variant causes a missense change. The variant allele was found at a frequency of 0.152 in 1,613,636 control chromosomes in the GnomAD database, including 21,434 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 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 0.14 (1871 hom., cov: 32)
  • Exomes 𝑓: 0.15 (19563 hom.)
• Consequence: DISP3 NM_020780.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.46

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=0.002960056).
• BP6: Variant 1-11519447-G-C is Benign according to our data. Variant chr1-11519447-G-C is described in ClinVar as [Benign]. Clinvar id is 3059525.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISP3	NM_020780.2	c.1982G>C	p.Gly661Ala	missense_variant	8/21	ENST00000294484.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISP3	ENST00000294484.7	c.1982G>C	p.Gly661Ala	missense_variant	8/21	1	NM_020780.2	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21638 AN: 152120 Hom.: 1871 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.146

GnomAD3 exomes AF: 0.161 AC: 40130 AN: 249310 Hom.: 4388 AF XY: 0.163 AC XY: 22111 AN XY: 135302

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.0945

Gnomad ASJ exome AF: 0.162

Gnomad EAS exome AF: 0.465

Gnomad SAS exome AF: 0.199

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.148

GnomAD4 exome AF: 0.154 AC: 224326 AN: 1461398 Hom.: 19563 Cov.: 36 AF XY: 0.155 AC XY: 112956 AN XY: 727006

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.0971

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.159

GnomAD4 genome AF: 0.142 AC: 21635 AN: 152238 Hom.: 1871 Cov.: 32 AF XY: 0.144 AC XY: 10732 AN XY: 74426

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.148

Alfa AF: 0.139 Hom.: 478

Bravo AF: 0.141

TwinsUK AF: 0.142 AC: 527

ALSPAC AF: 0.146 AC: 563

ESP6500AA AF: 0.105 AC: 424

ESP6500EA AF: 0.144 AC: 1209

ExAC AF: 0.162 AC: 19622

Asia WGS AF: 0.316 AC: 1098 AN: 3478

EpiCase AF: 0.140

EpiControl AF: 0.139

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 21, 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	0.12
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	20
Dann	Benign	0.91
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	P;P
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.39	N
REVEL	Uncertain	0.30
Sift	Benign	0.33	T
Sift4G	Benign	0.28	T
Polyphen		0.52	P
Vest4		0.12
MPC		0.62
ClinPred		0.013	T
GERP RS		3.7
Varity_R		0.046
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: rs2072993; hg19: chr1-11579504; COSMIC: COSV53819871;