Variant rs3003609 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004408.4(DNM1):c.1008C>T(p.Phe336=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,613,764 control chromosomes in the GnomAD database, including 236,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 17223 hom., cov: 32)

Exomes 𝑓: 0.54 ( 219465 hom. )

Consequence

DNM1
NM_004408.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.579

Variant links:

Genes affected

DNM1 (HGNC:2972): (dynamin 1) This gene encodes a member of the dynamin subfamily of GTP-binding proteins. The encoded protein possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the encoded protein, which can also self-assemble leading to stimulation of GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, particularly on chromosomes Y and 15. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

DNM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 9-128222476-C-T is Benign according to our data. Variant chr9-128222476-C-T is described in ClinVar as [Benign]. Clinvar id is 380777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128222476-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.579 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM1	NM_004408.4 linkuse as main transcript	c.1008C>T	p.Phe336=	synonymous_variant	8/22	ENST00000372923.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM1	ENST00000372923.8 linkuse as main transcript	c.1008C>T	p.Phe336=	synonymous_variant	8/22	1	NM_004408.4	A1	Q05193-1

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65773

AN:

151902

Hom.:

17215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.659

Gnomad AMR

AF:

0.602

Gnomad ASJ

AF:

0.447

Gnomad EAS

AF:

0.588

Gnomad SAS

AF:

0.590

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.465

GnomAD3 exomes

AF:

0.542

AC:

136150

AN:

251218

Hom.:

39293

AF XY:

0.546

AC XY:

74113

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.707

Gnomad ASJ exome

AF:

0.443

Gnomad EAS exome

AF:

0.599

Gnomad SAS exome

AF:

0.582

Gnomad FIN exome

AF:

0.534

Gnomad NFE exome

AF:

0.543

Gnomad OTH exome

AF:

0.542

GnomAD4 exome

AF:

0.542

AC:

792635

AN:

1461744

Hom.:

219465

Cov.:

AF XY:

0.543

AC XY:

394906

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.692

Gnomad4 ASJ exome

AF:

0.439

Gnomad4 EAS exome

AF:

0.581

Gnomad4 SAS exome

AF:

0.581

Gnomad4 FIN exome

AF:

0.541

Gnomad4 NFE exome

AF:

0.549

Gnomad4 OTH exome

AF:

0.526

GnomAD4 genome

AF:

0.433

AC:

65779

AN:

152020

Hom.:

17223

Cov.:

AF XY:

0.439

AC XY:

32590

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.602

Gnomad4 ASJ

AF:

0.447

Gnomad4 EAS

AF:

0.588

Gnomad4 SAS

AF:

0.589

Gnomad4 FIN

AF:

0.531

Gnomad4 NFE

AF:

0.541

Gnomad4 OTH

AF:

0.465

Alfa

AF:

0.523

Hom.:

51107

Bravo

AF:

0.424

Asia WGS

AF:

0.570

AC:

1978

AN:

3478

EpiCase

AF:

0.540

EpiControl

AF:

0.543

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 88% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 82. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 06, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Developmental and epileptic encephalopathy, 31

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 31, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Athena Diagnostics

Apr 20, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

7.0

DANN

Benign

0.87

Splicing

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