12-32701432-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001278464.2(DNM1L):c.120A>C(p.Ser40Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,613,402 control chromosomes in the GnomAD database, including 15,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1569 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13597 hom. )

Consequence

DNM1L
NM_001278464.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0220

Publications

15 publications found

Variant links:

Genes affected

DNM1L (HGNC:2973): (dynamin 1 like) This gene encodes a member of the dynamin superfamily of GTPases. The encoded protein mediates mitochondrial and peroxisomal division, and is involved in developmentally regulated apoptosis and programmed necrosis. Dysfunction of this gene is implicated in several neurological disorders, including Alzheimer's disease. Mutations in this gene are associated with the autosomal dominant disorder, encephalopathy, lethal, due to defective mitochondrial and peroxisomal fission (EMPF). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]

DNM1L Gene-Disease associations (from GenCC):

encephalopathy due to mitochondrial and peroxisomal fission defect
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1
Inheritance: AD, AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
optic atrophy 5
Inheritance: AD Classification: STRONG Submitted by: G2P
autosomal dominant optic atrophy, classic form
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Leigh syndrome
Inheritance: AR, AD Classification: LIMITED Submitted by: ClinGen

DNM1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 12-32701432-A-C is Benign according to our data. Variant chr12-32701432-A-C is described in ClinVar as [Benign]. Clinvar id is 260165.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.022 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM1L	NM_001278464.2 link	c.120A>C	p.Ser40Ser	synonymous_variant	Exon 2 of 21	ENST00000553257.6	NP_001265393.1	O00429-6B4DYR6
DNM1L	NM_012062.5 link	c.120A>C	p.Ser40Ser	synonymous_variant	Exon 2 of 20	ENST00000549701.6	NP_036192.2	O00429-1B4DYR6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM1L	ENST00000553257.6 link	c.120A>C	p.Ser40Ser	synonymous_variant	Exon 2 of 21	2	NM_001278464.2	ENSP00000449089.1		O00429-6
DNM1L	ENST00000549701.6 link	c.120A>C	p.Ser40Ser	synonymous_variant	Exon 2 of 20	1	NM_012062.5	ENSP00000450399.1		O00429-1

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21519

AN:

152120

Hom.:

1565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.0733

Gnomad SAS

AF:

0.106

Gnomad FIN

AF:

0.0893

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.153

GnomAD2 exomes

AF:

0.123

AC:

30861

AN:

251266

AF XY:

0.125

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.0779

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.0769

Gnomad FIN exome

AF:

0.0971

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.134

AC:

196024

AN:

1461164

Hom.:

13597

Cov.:

AF XY:

0.134

AC XY:

97677

AN XY:

726940

show subpopulations

African (AFR)

AF:

0.175

AC:

5873

AN:

33470

American (AMR)

AF:

0.0837

AC:

3741

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

4240

AN:

26130

East Asian (EAS)

AF:

0.0709

AC:

2814

AN:

39692

South Asian (SAS)

AF:

0.112

AC:

9652

AN:

86244

European-Finnish (FIN)

AF:

0.100

AC:

5345

AN:

53412

Middle Eastern (MID)

AF:

0.180

AC:

1038

AN:

5766

European-Non Finnish (NFE)

AF:

0.139

AC:

154915

AN:

1111378

Other (OTH)

AF:

0.139

AC:

8406

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

8026

16051

24077

32102

40128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.141

AC:

21524

AN:

152238

Hom.:

1569

Cov.:

AF XY:

0.139

AC XY:

10346

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.169

AC:

7033

AN:

41544

American (AMR)

AF:

0.122

AC:

1867

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

559

AN:

3468

East Asian (EAS)

AF:

0.0734

AC:

380

AN:

5174

South Asian (SAS)

AF:

0.106

AC:

509

AN:

4822

European-Finnish (FIN)

AF:

0.0893

AC:

948

AN:

10612

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.141

AC:

9606

AN:

68000

Other (OTH)

AF:

0.151

AC:

319

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

939

1879

2818

3758

4697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.145

Hom.:

3179

Bravo

AF:

0.146

Asia WGS

AF:

0.105

AC:

366

AN:

3476

EpiCase

AF:

0.149

EpiControl

AF:

0.153

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 22, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2022

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The p.Ser40Ser variant in DNM1L is classified as benign because it has been identified in 12.4% of total chromosomes in gnomAD, including 2316 homozygous individuals (https://gnomad.broadinstitute.org/). -

Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Optic atrophy 5

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.6

(source)

DANN

Benign

0.76

PhyloP100

0.022

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=91/9

polymorphism (auto)

(source)

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

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12-32701432-A-C

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