Variant 1-172038413-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015569.5(DNM3):c.944A>C(p.Lys315Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,476 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 1 hom. )

Consequence

DNM3
NM_015569.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.98

Variant links:

Genes affected

DNM3 (HGNC:29125): (dynamin 3) This gene encodes a member of a family of guanosine triphosphate (GTP)-binding proteins that associate with microtubules and are involved in vesicular transport. The encoded protein functions in the development of megakaryocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

DNM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM3	NM_015569.5 linkuse as main transcript	c.944A>C	p.Lys315Thr	missense_variant	7/21	ENST00000627582.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM3	ENST00000627582.3 linkuse as main transcript	c.944A>C	p.Lys315Thr	missense_variant	7/21	1	NM_015569.5	A1	Q9UQ16-3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000482

AC:

AN:

248994

Hom.:

AF XY:

0.0000666

AC XY:

AN XY:

135060

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:

0.000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461158

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

726880

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:

0.000301

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00103

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

ExAC

AF:

0.0000497

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2023

The c.944A>C (p.K315T) alteration is located in exon 7 (coding exon 7) of the DNM3 gene. This alteration results from a A to C substitution at nucleotide position 944, causing the lysine (K) at amino acid position 315 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.20

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.91

LIST_S2

Pathogenic

0.98

D;D;D;D;D;D

M_CAP

Benign

0.060

MetaRNN

Uncertain

0.46

T;T;T;T;T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Pathogenic

3.1

M;M;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-5.4

D;D;.;D;D;D

REVEL

Uncertain

0.41

Sift

Benign

0.043

D;D;.;D;D;D

Sift4G

Uncertain

0.016

D;T;T;T;D;D

Polyphen

0.54, 0.70, 0.11

.;.;P;P;B;.

Vest4

0.36

MutPred

0.51

Loss of methylation at K315 (P = 0.0098);Loss of methylation at K315 (P = 0.0098);Loss of methylation at K315 (P = 0.0098);Loss of methylation at K315 (P = 0.0098);Loss of methylation at K315 (P = 0.0098);.;

MVP

0.79

ClinPred

0.58

GERP RS

2.6

Varity_R

0.59

gMVP

0.55

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