dbSNP rs368835504: DNM1:c.-17C>A (chr9-128203454-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004408.4(DNM1):c.-17C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000945 in 1,461,992 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 10 hom., cov: 31)

Exomes 𝑓: 0.00048 ( 6 hom. )

Consequence

DNM1
NM_004408.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.706

Publications

0 publications found

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:

CIZ1 (HGNC:16744): (CDKN1A interacting zinc finger protein 1) The protein encoded by this gene is a zinc finger DNA binding protein that interacts with CIP1, part of a complex with cyclin E. The encoded protein may regulate the cellular localization of CIP1. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

CIZ1 Gene-Disease associations (from GenCC):

dystonia 23
Inheritance: Unknown Classification: MODERATE Submitted by: Genomics England PanelApp
inherited dystonia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

CIZ1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 9-128203454-C-A is Benign according to our data. Variant chr9-128203454-C-A is described in ClinVar as Benign. ClinVar VariationId is 384406.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00498 (755/151586) while in subpopulation AFR AF = 0.0174 (720/41494). AF 95% confidence interval is 0.0163. There are 10 homozygotes in GnomAd4. There are 348 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004408.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNM1	NM_004408.4	MANE Select	c.-17C>A	5_prime_UTR	Exon 1 of 22	NP_004399.2	Q05193-1
DNM1	NM_001374269.1		c.-17C>A	5_prime_UTR	Exon 1 of 22	NP_001361198.1	A0A994J7J4
DNM1	NM_001288739.2		c.-17C>A	5_prime_UTR	Exon 1 of 22	NP_001275668.1	Q05193-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNM1	ENST00000372923.8	TSL:1 MANE Select	c.-17C>A	5_prime_UTR	Exon 1 of 22	ENSP00000362014.4	Q05193-1
DNM1	ENST00000486160.3	TSL:1	c.-17C>A	5_prime_UTR	Exon 1 of 22	ENSP00000420045.1	Q05193-2
DNM1	ENST00000341179.11	TSL:1	c.-17C>A	5_prime_UTR	Exon 1 of 23	ENSP00000345680.7	Q05193-3

Frequencies

GnomAD3 genomes

AF:

0.00498

AC:

755

AN:

151478

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00184

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00336

GnomAD2 exomes

AF:

0.000546

AC:

AN:

91504

AF XY:

0.000417

show subpopulations

Gnomad AFR exome

AF:

0.0192

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000276

Gnomad OTH exome

AF:

0.000416

GnomAD4 exome

AF:

0.000478

AC:

626

AN:

1310406

Hom.:

Cov.:

AF XY:

0.000435

AC XY:

281

AN XY:

645962

show subpopulations

African (AFR)

AF:

0.0199

AC:

531

AN:

26700

American (AMR)

AF:

0.000845

AC:

AN:

24838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22688

East Asian (EAS)

AF:

0.00

AC:

AN:

27736

South Asian (SAS)

AF:

0.0000833

AC:

AN:

72014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40626

Middle Eastern (MID)

AF:

0.000415

AC:

AN:

4816

European-Non Finnish (NFE)

AF:

0.00000386

AC:

AN:

1037536

Other (OTH)

AF:

0.00116

AC:

AN:

53452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

122

152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00498

AC:

755

AN:

151586

Hom.:

Cov.:

AF XY:

0.00470

AC XY:

348

AN XY:

74062

show subpopulations

African (AFR)

AF:

0.0174

AC:

720

AN:

41494

American (AMR)

AF:

0.00177

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67698

Other (OTH)

AF:

0.00333

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

109

145

181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00465

Hom.:

Bravo

AF:

0.00592

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

0.71

PromoterAI

-0.043

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over