9-128222530-C-T

Position:

chr9-128222530-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004408.4(DNM1):c.1062C>T(p.Tyr354Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 1,614,074 control chromosomes in the GnomAD database, including 5,349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 517 hom., cov: 32)

Exomes 𝑓: 0.079 ( 4832 hom. )

Consequence

DNM1
NM_004408.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.607

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 9-128222530-C-T is Benign according to our data. Variant chr9-128222530-C-T is described in ClinVar as [Benign]. Clinvar id is 380913.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.607 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNM1	NM_004408.4 linkuse as main transcript	c.1062C>T	p.Tyr354Tyr	synonymous_variant	8/22	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.1062C>T	p.Tyr354Tyr	synonymous_variant	8/22	1	NM_004408.4	ENSP00000362014.4		Q05193-1
DNM1	ENST00000634267.2 linkuse as main transcript	c.1062C>T	p.Tyr354Tyr	synonymous_variant	8/22	5		ENSP00000489096.1		A0A0U1RQP1

Frequencies

GnomAD3 genomes

AF:

0.0808

AC:

12295

AN:

152106

Hom.:

515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0638

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.0905

Gnomad FIN

AF:

0.0576

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0778

Gnomad OTH

AF:

0.0850

GnomAD3 exomes

AF:

0.0690

AC:

17352

AN:

251424

Hom.:

686

AF XY:

0.0708

AC XY:

9623

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.0430

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.00234

Gnomad SAS exome

AF:

0.0907

Gnomad FIN exome

AF:

0.0574

Gnomad NFE exome

AF:

0.0738

Gnomad OTH exome

AF:

0.0797

GnomAD4 exome

AF:

0.0788

AC:

115146

AN:

1461850

Hom.:

4832

Cov.:

AF XY:

0.0796

AC XY:

57886

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.0456

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.00222

Gnomad4 SAS exome

AF:

0.0913

Gnomad4 FIN exome

AF:

0.0588

Gnomad4 NFE exome

AF:

0.0806

Gnomad4 OTH exome

AF:

0.0810

GnomAD4 genome

AF:

0.0808

AC:

12307

AN:

152224

Hom.:

517

Cov.:

AF XY:

0.0790

AC XY:

5880

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0636

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.00252

Gnomad4 SAS

AF:

0.0912

Gnomad4 FIN

AF:

0.0576

Gnomad4 NFE

AF:

0.0778

Gnomad4 OTH

AF:

0.0855

Alfa

AF:

0.0827

Hom.:

361

Bravo

AF:

0.0815

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

EpiCase

AF:

0.0763

EpiControl

AF:

0.0772

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 05, 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. -

Developmental and epileptic encephalopathy, 31A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

5.8

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over