Variant 12-32679332-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001278464.2(DNM1L):c.-32G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,484,520 control chromosomes in the GnomAD database, including 538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.036 ( 265 hom., cov: 33)

Exomes 𝑓: 0.011 ( 273 hom. )

Consequence

DNM1L
NM_001278464.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.581

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 12-32679332-G-T is Benign according to our data. Variant chr12-32679332-G-T is described in ClinVar as [Benign]. Clinvar id is 137129.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM1L	NM_001278464.2 linkuse as main transcript	c.-32G>T		5_prime_UTR_variant	1/21	ENST00000553257.6
DNM1L	NM_012062.5 linkuse as main transcript	c.-32G>T		5_prime_UTR_variant	1/20	ENST00000549701.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM1L	ENST00000549701.6 linkuse as main transcript	c.-32G>T		5_prime_UTR_variant	1/20	1	NM_012062.5		O00429-1
DNM1L	ENST00000553257.6 linkuse as main transcript	c.-32G>T		5_prime_UTR_variant	1/21	2	NM_001278464.2		O00429-6

Frequencies

GnomAD3 genomes

AF:

0.0359

AC:

5459

AN:

152242

Hom.:

263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00791

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0132

AC:

3126

AN:

236356

Hom.:

104

AF XY:

0.0113

AC XY:

1455

AN XY:

128482

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.00866

Gnomad ASJ exome

AF:

0.00307

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00376

Gnomad FIN exome

AF:

0.00105

Gnomad NFE exome

AF:

0.00877

Gnomad OTH exome

AF:

0.00690

GnomAD4 exome

AF:

0.0109

AC:

14519

AN:

1332160

Hom.:

273

Cov.:

AF XY:

0.0105

AC XY:

7019

AN XY:

669320

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.0101

Gnomad4 ASJ exome

AF:

0.00321

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00407

Gnomad4 FIN exome

AF:

0.000791

Gnomad4 NFE exome

AF:

0.00942

Gnomad4 OTH exome

AF:

0.0143

GnomAD4 genome

AF:

0.0359

AC:

5475

AN:

152360

Hom.:

265

Cov.:

AF XY:

0.0348

AC XY:

2591

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.0183

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.00791

Gnomad4 OTH

AF:

0.0274

Alfa

AF:

0.00803

Hom.:

Bravo

AF:

0.0407

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 26, 2013

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

Cadd

Benign

7.3

Dann

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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