1-11516149-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_020780.2(DISP3):c.1737C>T(p.Asn579=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00377 in 1,613,980 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (62 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (79 hom.)
• Consequence: DISP3 NM_020780.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.19

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 1-11516149-C-T is Benign according to our data. Variant chr1-11516149-C-T is described in ClinVar as [Benign]. Clinvar id is 775509.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DISP3	NM_020780.2	c.1737C>T	p.Asn579=	synonymous_variant	6/21	ENST00000294484.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DISP3	ENST00000294484.7	c.1737C>T	p.Asn579=	synonymous_variant	6/21	1	NM_020780.2	P1

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2658 AN: 152198 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0582

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00745

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0167

GnomAD3 exomes AF: 0.00536 AC: 1336 AN: 249060 Hom.: 20 AF XY: 0.00416 AC XY: 562 AN XY: 135130

Gnomad AFR exome AF: 0.0606

Gnomad AMR exome AF: 0.00302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0126

Gnomad SAS exome AF: 0.000491

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.00380

GnomAD4 exome AF: 0.00235 AC: 3429 AN: 1461664 Hom.: 79 Cov.: 31 AF XY: 0.00208 AC XY: 1510 AN XY: 727154

Gnomad4 AFR exome AF: 0.0645

Gnomad4 AMR exome AF: 0.00351

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0147

Gnomad4 SAS exome AF: 0.000417

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000132

Gnomad4 OTH exome AF: 0.00530

GnomAD4 genome AF: 0.0175 AC: 2661 AN: 152316 Hom.: 62 Cov.: 32 AF XY: 0.0168 AC XY: 1252 AN XY: 74482

Gnomad4 AFR AF: 0.0581

Gnomad4 AMR AF: 0.00745

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0165

Alfa AF: 0.00480 Hom.: 20

Bravo AF: 0.0205

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000545

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 25, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	6.3
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17036950; hg19: chr1-11576206; COSMIC: COSV53837646;