1-11501143-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020780.2(DISP3):c.151C>G(p.Leu51Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,613,926 control chromosomes in the GnomAD database, including 19 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 0.0013 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (15 hom.)
• Consequence: DISP3 NM_020780.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.104

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027417839).
• BP6: Variant 1-11501143-C-G is Benign according to our data. Variant chr1-11501143-C-G is described in ClinVar as [Benign]. Clinvar id is 721203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00133 (203/152288) while in subpopulation EAS AF= 0.0244 (126/5162). AF 95% confidence interval is 0.0209. There are 4 homozygotes in gnomad4. There are 107 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISP3	NM_020780.2	c.151C>G	p.Leu51Val	missense_variant	2/21	ENST00000294484.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISP3	ENST00000294484.7	c.151C>G	p.Leu51Val	missense_variant	2/21	1	NM_020780.2	P1
	ENST00000649975.1	n.711G>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.00133 AC: 203 AN: 152170 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.0244

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00351 AC: 873 AN: 248574 Hom.: 9 AF XY: 0.00309 AC XY: 417 AN XY: 134912

Gnomad AFR exome AF: 0.000583

Gnomad AMR exome AF: 0.0106

Gnomad ASJ exome AF: 0.00340

Gnomad EAS exome AF: 0.0237

Gnomad SAS exome AF: 0.000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000533

Gnomad OTH exome AF: 0.00232

GnomAD4 exome AF: 0.00106 AC: 1547 AN: 1461638 Hom.: 15 Cov.: 31 AF XY: 0.00102 AC XY: 739 AN XY: 727118

Gnomad4 AFR exome AF: 0.000358

Gnomad4 AMR exome AF: 0.00888

Gnomad4 ASJ exome AF: 0.00257

Gnomad4 EAS exome AF: 0.0228

Gnomad4 SAS exome AF: 0.000499

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000360

Gnomad4 OTH exome AF: 0.00132

GnomAD4 genome AF: 0.00133 AC: 203 AN: 152288 Hom.: 4 Cov.: 32 AF XY: 0.00144 AC XY: 107 AN XY: 74454

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.0244

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000893 Hom.: 0

Bravo AF: 0.00197

ExAC AF: 0.00309 AC: 373

Asia WGS AF: 0.0120 AC: 40 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

DISP3-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 13, 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	0.067
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	4.3
Dann	Benign	0.90
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.017
Sift	Benign	0.042	D
Sift4G	Benign	0.19	T
Polyphen		0.18	B
Vest4		0.13
MVP		0.076
MPC		0.55
ClinPred		0.0059	T
GERP RS		-1.7
Varity_R		0.069
gMVP		0.18

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: rs3738159; hg19: chr1-11561200;