rs35048348

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004408.4(DNM1):c.1062C>T(p.Tyr354Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 1,614,074 control chromosomes in the GnomAD database, including 5,349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 517 hom., cov: 32)

Exomes 𝑓: 0.079 ( 4832 hom. )

Consequence

DNM1
NM_004408.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.607

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 31A
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
developmental and epileptic encephalopathy, 31B
Inheritance: AR, AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
Lennox-Gastaut syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 9-128222530-C-T is Benign according to our data. Variant chr9-128222530-C-T is described in ClinVar as Benign. ClinVar VariationId is 380913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.607 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM1	NM_004408.4 link	c.1062C>T	p.Tyr354Tyr	synonymous_variant	Exon 8 of 22	ENST00000372923.8	NP_004399.2	Q05193-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM1	ENST00000372923.8 link	c.1062C>T	p.Tyr354Tyr	synonymous_variant	Exon 8 of 22	1	NM_004408.4	ENSP00000362014.4		Q05193-1
DNM1	ENST00000634267.2 link	c.1062C>T	p.Tyr354Tyr	synonymous_variant	Exon 8 of 22	5		ENSP00000489096.1		A0A0U1RQP1

Frequencies

GnomAD3 genomes

AF:

0.0808

AC:

12295

AN:

152106

Hom.:

515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0638

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.0905

Gnomad FIN

AF:

0.0576

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0778

Gnomad OTH

AF:

0.0850

GnomAD2 exomes

AF:

0.0690

AC:

17352

AN:

251424

AF XY:

0.0708

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.0430

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.00234

Gnomad FIN exome

AF:

0.0574

Gnomad NFE exome

AF:

0.0738

Gnomad OTH exome

AF:

0.0797

GnomAD4 exome

AF:

0.0788

AC:

115146

AN:

1461850

Hom.:

4832

Cov.:

AF XY:

0.0796

AC XY:

57886

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.110

AC:

3687

AN:

33478

American (AMR)

AF:

0.0456

AC:

2039

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

3244

AN:

26136

East Asian (EAS)

AF:

0.00222

AC:

AN:

39700

South Asian (SAS)

AF:

0.0913

AC:

7877

AN:

86258

European-Finnish (FIN)

AF:

0.0588

AC:

3139

AN:

53406

Middle Eastern (MID)

AF:

0.103

AC:

596

AN:

5768

European-Non Finnish (NFE)

AF:

0.0806

AC:

89584

AN:

1111986

Other (OTH)

AF:

0.0810

AC:

4892

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

6048

12096

18145

24193

30241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3402

6804

10206

13608

17010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0808

AC:

12307

AN:

152224

Hom.:

517

Cov.:

AF XY:

0.0790

AC XY:

5880

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.104

AC:

4334

AN:

41526

American (AMR)

AF:

0.0636

AC:

973

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

421

AN:

3472

East Asian (EAS)

AF:

0.00252

AC:

AN:

5162

South Asian (SAS)

AF:

0.0912

AC:

440

AN:

4826

European-Finnish (FIN)

AF:

0.0576

AC:

611

AN:

10614

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0778

AC:

5290

AN:

68004

Other (OTH)

AF:

0.0855

AC:

181

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

572

1144

1715

2287

2859

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0797

Hom.:

613

Bravo

AF:

0.0815

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

EpiCase

AF:

0.0763

EpiControl

AF:

0.0772

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jan 05, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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, 31A

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 16, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

5.8

(source)

DANN

Benign

0.91

PhyloP100

-0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=91/9

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over