Variant rs145318071 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_004408.4(DNM1):c.1707C>G(p.Asn569Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N569N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DNM1
NM_004408.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.12

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 links:

DNM1 (HGNC:):

DNM1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DNM1. . Gene score misZ 5.1795 (greater than the threshold 3.09). Trascript score misZ 5.021 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy, 31, undetermined early-onset epileptic encephalopathy, developmental and epileptic encephalopathy 31B, developmental and epileptic encephalopathy, Lennox-Gastaut syndrome.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNM1	NM_004408.4 linkuse as main transcript	c.1707C>G	p.Asn569Lys	missense_variant	16/22	ENST00000372923.8	NP_004399.2	Q05193-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNM1	ENST00000372923.8 linkuse as main transcript	c.1707C>G	p.Asn569Lys	missense_variant	16/22	1	NM_004408.4	ENSP00000362014.4		Q05193-1
DNM1	ENST00000634267.2 linkuse as main transcript	c.1707C>G	p.Asn569Lys	missense_variant	16/22	5		ENSP00000489096.1		A0A0U1RQP1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251480

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.75

D;.;.;.;.;.;T;.;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.97

D;.;.;D;D;D;D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.69

D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.6

M;M;M;M;.;M;.;M;.

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.1

D;D;D;D;.;D;.;.;.

REVEL

Uncertain

0.30

Sift

Benign

0.13

T;D;D;D;.;T;.;.;.

Sift4G

Benign

0.27

T;T;T;T;T;T;T;T;T

Polyphen

0.89

P;.;P;.;.;.;.;P;.

Vest4

0.72

MutPred

0.54

Loss of ubiquitination at K571 (P = 0.0328);Loss of ubiquitination at K571 (P = 0.0328);Loss of ubiquitination at K571 (P = 0.0328);Loss of ubiquitination at K571 (P = 0.0328);.;Loss of ubiquitination at K571 (P = 0.0328);.;Loss of ubiquitination at K571 (P = 0.0328);Loss of ubiquitination at K571 (P = 0.0328);

MVP

0.75

MPC

2.0

ClinPred

0.97

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.41

gMVP

0.64

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over