Variant 1-172388786-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_015569.5(DNM3):c.2499G>A(p.Thr833=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,592,604 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 80 hom. )

Consequence

DNM3
NM_015569.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.01

Variant links:

Genes affected

DNM3 (HGNC:29125): (dynamin 3) This gene encodes a member of a family of guanosine triphosphate (GTP)-binding proteins that associate with microtubules and are involved in vesicular transport. The encoded protein functions in the development of megakaryocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

DNM3 links:

PIGC (HGNC:8960): (phosphatidylinositol glycan anchor biosynthesis class C) This gene encodes an endoplasmic reticulum associated protein that is involved in glycosylphosphatidylinositol (GPI) lipid anchor biosynthesis. The GPI lipid anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. The encoded protein is one subunit of the GPI N-acetylglucosaminyl (GlcNAc) transferase that transfers GlcNAc to phosphatidylinositol (PI) on the cytoplasmic side of the endoplasmic reticulum. Two alternatively spliced transcripts that encode the same protein have been found for this gene. A pseudogene on chromosome 11 has also been characterized. [provided by RefSeq, Jul 2008]

PIGC links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 1-172388786-G-A is Benign according to our data. Variant chr1-172388786-G-A is described in ClinVar as [Benign]. Clinvar id is 715436.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-4.01 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM3	NM_015569.5 linkuse as main transcript	c.2499G>A	p.Thr833=	synonymous_variant	20/21	ENST00000627582.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM3	ENST00000627582.3 linkuse as main transcript	c.2499G>A	p.Thr833=	synonymous_variant	20/21	1	NM_015569.5	A1	Q9UQ16-3

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

389

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0544

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00503

AC:

1050

AN:

208622

Hom.:

AF XY:

0.00469

AC XY:

528

AN XY:

112608

show subpopulations

Gnomad AFR exome

AF:

0.0000859

Gnomad AMR exome

AF:

0.000165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0580

Gnomad SAS exome

AF:

0.000687

Gnomad FIN exome

AF:

0.00700

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.00263

GnomAD4 exome

AF:

0.00206

AC:

2966

AN:

1440254

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

1469

AN XY:

714462

show subpopulations

Gnomad4 AFR exome

AF:

0.000122

Gnomad4 AMR exome

AF:

0.000216

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0581

Gnomad4 SAS exome

AF:

0.000651

Gnomad4 FIN exome

AF:

0.00615

Gnomad4 NFE exome

AF:

0.000204

Gnomad4 OTH exome

AF:

0.00211

GnomAD4 genome

AF:

0.00255

AC:

389

AN:

152350

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

216

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0547

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00565

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000559

Hom.:

Bravo

AF:

0.00232

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 14, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.023

DANN

Benign

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over