Variant 12-32679339-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_012062.5(DNM1L):c.-25A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000436 in 1,569,678 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

DNM1L
NM_012062.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.135

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 12-32679339-A-G is Benign according to our data. Variant chr12-32679339-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 308384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00211 (321/152162) while in subpopulation AFR AF= 0.00698 (290/41538). AF 95% confidence interval is 0.00632. There are 1 homozygotes in gnomad4. There are 170 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNM1L	NM_001278464.2 link	c.-25A>G		5_prime_UTR_variant	1/21	ENST00000553257.6	NP_001265393.1	O00429-6B4DYR6
DNM1L	NM_012062.5 link	c.-25A>G		5_prime_UTR_variant	1/20	ENST00000549701.6	NP_036192.2	O00429-1B4DYR6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNM1L	ENST00000553257 link	c.-25A>G		5_prime_UTR_variant	1/21	2	NM_001278464.2	ENSP00000449089.1		O00429-6
DNM1L	ENST00000549701 link	c.-25A>G		5_prime_UTR_variant	1/20	1	NM_012062.5	ENSP00000450399.1		O00429-1

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

317

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00691

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000567

AC:

136

AN:

239940

Hom.:

AF XY:

0.000406

AC XY:

AN XY:

130452

show subpopulations

Gnomad AFR exome

AF:

0.00744

Gnomad AMR exome

AF:

0.000327

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000335

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000466

Gnomad OTH exome

AF:

0.000853

GnomAD4 exome

AF:

0.000257

AC:

364

AN:

1417516

Hom.:

Cov.:

AF XY:

0.000213

AC XY:

151

AN XY:

707482

show subpopulations

Gnomad4 AFR exome

AF:

0.00614

Gnomad4 AMR exome

AF:

0.000386

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.000510

GnomAD4 genome

AF:

0.00211

AC:

321

AN:

152162

Hom.:

Cov.:

AF XY:

0.00228

AC XY:

170

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00698

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.00260

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 30, 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. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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