chr12-32733738-A-G

Position:

chr12-32733738-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000549701.6(DNM1L):c.1470A>G(p.Glu490=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,920 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 6 hom., cov: 33)

Exomes 𝑓: 0.010 ( 84 hom. )

Consequence

DNM1L
ENST00000549701.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.26

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:

YARS2 (HGNC:24249): (tyrosyl-tRNA synthetase 2) This gene encodes a mitochondrial protein that catalyzes the attachment of tyrosine to tRNA(Tyr). Mutations in this gene are associated with myopathy with lactic acidosis and sideroblastic anemia type 2 (MLASA2). [provided by RefSeq, Jan 2011]

YARS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 12-32733738-A-G is Benign according to our data. Variant chr12-32733738-A-G is described in ClinVar as [Benign]. Clinvar id is 137127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.26 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00802 (1222/152330) while in subpopulation NFE AF= 0.0122 (830/68030). AF 95% confidence interval is 0.0115. There are 6 homozygotes in gnomad4. There are 566 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNM1L	NM_001278464.2 linkuse as main transcript	c.1509A>G	p.Glu503=	synonymous_variant	14/21	ENST00000553257.6	NP_001265393.1
DNM1L	NM_012062.5 linkuse as main transcript	c.1470A>G	p.Glu490=	synonymous_variant	13/20	ENST00000549701.6	NP_036192.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNM1L	ENST00000553257.6 linkuse as main transcript	c.1509A>G	p.Glu503=	synonymous_variant	14/21	2	NM_001278464.2	ENSP00000449089		O00429-6
DNM1L	ENST00000549701.6 linkuse as main transcript	c.1470A>G	p.Glu490=	synonymous_variant	13/20	1	NM_012062.5	ENSP00000450399		O00429-1

Frequencies

GnomAD3 genomes

AF:

0.00804

AC:

1224

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00277

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00877

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00227

Gnomad FIN

AF:

0.00622

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00779

AC:

1959

AN:

251334

Hom.:

AF XY:

0.00819

AC XY:

1113

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00717

Gnomad ASJ exome

AF:

0.00873

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00317

Gnomad FIN exome

AF:

0.00628

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00995

GnomAD4 exome

AF:

0.0104

AC:

15271

AN:

1461590

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

7486

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.00218

Gnomad4 AMR exome

AF:

0.00778

Gnomad4 ASJ exome

AF:

0.00815

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00322

Gnomad4 FIN exome

AF:

0.00730

Gnomad4 NFE exome

AF:

0.0119

Gnomad4 OTH exome

AF:

0.0114

GnomAD4 genome

AF:

0.00802

AC:

1222

AN:

152330

Hom.:

Cov.:

AF XY:

0.00760

AC XY:

566

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00277

Gnomad4 AMR

AF:

0.00876

Gnomad4 ASJ

AF:

0.00864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00622

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.00812

Asia WGS

AF:

0.00115

AC:

AN:

3476

EpiCase

AF:

0.0145

EpiControl

AF:

0.0141

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Aug 07, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 03, 2023	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	DNM1L: BP4, BP7, BS1, BS2 -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.6

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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