1-11501107-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.115G>A(p.Gly39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 1,613,808 control chromosomes in the GnomAD database, including 10,523 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 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 0.15 (2957 hom., cov: 32)
  • Exomes 𝑓: 0.084 (7566 hom.)
• Consequence: DISP3 NM_020780.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.89

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005902976).
• BP6: Variant 1-11501107-G-A is Benign according to our data. Variant chr1-11501107-G-A is described in ClinVar as [Benign]. Clinvar id is 3060426.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISP3	NM_020780.2	c.115G>A	p.Gly39Arg	missense_variant	2/21	ENST00000294484.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISP3	ENST00000294484.7	c.115G>A	p.Gly39Arg	missense_variant	2/21	1	NM_020780.2	P1
	ENST00000649975.1	n.747C>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23393 AN: 151996 Hom.: 2952 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0746

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0448

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0680

Gnomad OTH AF: 0.124

GnomAD3 exomes AF: 0.105 AC: 26245 AN: 249026 Hom.: 2273 AF XY: 0.108 AC XY: 14608 AN XY: 135148

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.0451

Gnomad ASJ exome AF: 0.119

Gnomad EAS exome AF: 0.0385

Gnomad SAS exome AF: 0.204

Gnomad FIN exome AF: 0.123

Gnomad NFE exome AF: 0.0702

Gnomad OTH exome AF: 0.0815

GnomAD4 exome AF: 0.0841 AC: 122880 AN: 1461694 Hom.: 7566 Cov.: 31 AF XY: 0.0872 AC XY: 63373 AN XY: 727156

Gnomad4 AFR exome AF: 0.354

Gnomad4 AMR exome AF: 0.0484

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.0405

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.0663

Gnomad4 OTH exome AF: 0.0996

GnomAD4 genome AF: 0.154 AC: 23423 AN: 152114 Hom.: 2957 Cov.: 32 AF XY: 0.155 AC XY: 11562 AN XY: 74382

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.0745

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0447

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0680

Gnomad4 OTH AF: 0.122

Alfa AF: 0.0824 Hom.: 1248

Bravo AF: 0.153

TwinsUK AF: 0.0707 AC: 262

ALSPAC AF: 0.0752 AC: 290

ESP6500AA AF: 0.337 AC: 1260

ESP6500EA AF: 0.0664 AC: 543

ExAC AF: 0.112 AC: 13513

Asia WGS AF: 0.147 AC: 512 AN: 3478

EpiCase AF: 0.0726

EpiControl AF: 0.0679

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
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	4.4
Dann	Benign	0.20
DEOGEN2	Benign	0.0091	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.059
Sift	Benign	0.57	T
Sift4G	Benign	0.078	T
Polyphen		0.0	B
Vest4		0.050
MutPred		0.15		Gain of solvent accessibility (P = 0.019);
MPC		0.44
ClinPred		0.0050	T
GERP RS		4.8
Varity_R		0.065
gMVP		0.16

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: rs41274528; hg19: chr1-11561164; COSMIC: COSV53821927;