NM_004408.4:c.1493+14delC

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_004408.4(DNM1):​c.1493+14delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000597 in 1,609,628 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00062 ( 4 hom. )

Consequence

DNM1
NM_004408.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.57

Publications

0 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP6
Variant 9-128239524-TC-T is Benign according to our data. Variant chr9-128239524-TC-T is described in ClinVar as Benign. ClinVar VariationId is 476061.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAdExome4 at 4 AR,AD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNM1NM_004408.4 linkc.1493+14delC intron_variant Intron 12 of 21 ENST00000372923.8 NP_004399.2 Q05193-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNM1ENST00000372923.8 linkc.1493+10delC intron_variant Intron 12 of 21 1 NM_004408.4 ENSP00000362014.4 Q05193-1
DNM1ENST00000634267.2 linkc.1493+10delC intron_variant Intron 12 of 21 5 ENSP00000489096.1 A0A0U1RQP1

Frequencies

GnomAD3 genomes
AF:
0.000414
AC:
62
AN:
149584
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000248
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000671
Gnomad ASJ
AF:
0.00233
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00443
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000429
Gnomad OTH
AF:
0.000973
GnomAD2 exomes
AF:
0.00102
AC:
255
AN:
251058
AF XY:
0.00112
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000203
Gnomad ASJ exome
AF:
0.00278
Gnomad EAS exome
AF:
0.000109
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000484
Gnomad OTH exome
AF:
0.00245
GnomAD4 exome
AF:
0.000616
AC:
899
AN:
1459934
Hom.:
4
Cov.:
32
AF XY:
0.000716
AC XY:
520
AN XY:
726232
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33420
American (AMR)
AF:
0.000246
AC:
11
AN:
44634
Ashkenazi Jewish (ASJ)
AF:
0.00268
AC:
70
AN:
26094
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39652
South Asian (SAS)
AF:
0.00485
AC:
418
AN:
86178
European-Finnish (FIN)
AF:
0.0000187
AC:
1
AN:
53376
Middle Eastern (MID)
AF:
0.00590
AC:
34
AN:
5760
European-Non Finnish (NFE)
AF:
0.000269
AC:
299
AN:
1110520
Other (OTH)
AF:
0.00106
AC:
64
AN:
60300
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.491
Heterozygous variant carriers
0
48
96
145
193
241
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.000414
AC:
62
AN:
149694
Hom.:
0
Cov.:
31
AF XY:
0.000439
AC XY:
32
AN XY:
72974
show subpopulations
African (AFR)
AF:
0.0000247
AC:
1
AN:
40472
American (AMR)
AF:
0.0000671
AC:
1
AN:
14914
Ashkenazi Jewish (ASJ)
AF:
0.00233
AC:
8
AN:
3432
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5092
South Asian (SAS)
AF:
0.00443
AC:
21
AN:
4736
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10194
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
290
European-Non Finnish (NFE)
AF:
0.000429
AC:
29
AN:
67578
Other (OTH)
AF:
0.000962
AC:
2
AN:
2078
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.493
Heterozygous variant carriers
0
3
5
8
10
13
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000781
Hom.:
0
Bravo
AF:
0.000359
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Apr 01, 2025
CeGaT Center for Human Genetics Tuebingen
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

DNM1: BS1, BS2 -

Apr 20, 2016
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Developmental and epileptic encephalopathy, 31A Benign:1
Jan 30, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.6
Mutation Taster
=100/0
polymorphism

Splicing

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

Publications

Other links and lift over

dbSNP: rs371426966; hg19: chr9-131001803; API