1-11516037-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_020780.2(DISP3):c.1625G>A(p.Arg542His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00443 in 1,613,970 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (26 hom.)
• Consequence: DISP3 NM_020780.2 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.92

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024115264).
• BP6: Variant 1-11516037-G-A is Benign according to our data. Variant chr1-11516037-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 782971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISP3	NM_020780.2	c.1625G>A	p.Arg542His	missense_variant	6/21	ENST00000294484.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISP3	ENST00000294484.7	c.1625G>A	p.Arg542His	missense_variant	6/21	1	NM_020780.2	P1

Frequencies

GnomAD3 genomes AF: 0.00336 AC: 511 AN: 152064 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00579

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00289 AC: 720 AN: 249182 Hom.: 5 AF XY: 0.00300 AC XY: 406 AN XY: 135196

Gnomad AFR exome AF: 0.000711

Gnomad AMR exome AF: 0.00246

Gnomad ASJ exome AF: 0.000597

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.000425

Gnomad FIN exome AF: 0.00116

Gnomad NFE exome AF: 0.00489

Gnomad OTH exome AF: 0.00430

GnomAD4 exome AF: 0.00454 AC: 6633 AN: 1461788 Hom.: 26 Cov.: 31 AF XY: 0.00453 AC XY: 3296 AN XY: 727198

Gnomad4 AFR exome AF: 0.000896

Gnomad4 AMR exome AF: 0.00237

Gnomad4 ASJ exome AF: 0.00126

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.00124

Gnomad4 NFE exome AF: 0.00552

Gnomad4 OTH exome AF: 0.00369

GnomAD4 genome AF: 0.00336 AC: 511 AN: 152182 Hom.: 1 Cov.: 32 AF XY: 0.00315 AC XY: 234 AN XY: 74400

Gnomad4 AFR AF: 0.000940

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00579

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00466 Hom.: 6

Bravo AF: 0.00314

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.000930 AC: 4

ESP6500EA AF: 0.00530 AC: 45

ExAC AF: 0.00262 AC: 318

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00387

EpiControl AF: 0.00563

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2023	DISP3: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 18, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Uncertain	0.13
Cadd	Pathogenic	32
Dann	Pathogenic	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.024	T
MetaSVM	Pathogenic	0.86	D
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.3	D
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.65
MVP		0.92
MPC		1.3
ClinPred		0.016	T
GERP RS		5.5
Varity_R		0.38
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs41274532; hg19: chr1-11576094; COSMIC: COSV53834257;