Genetic Variant DNM1:c.-15G>T (chr9-128203456-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_004408.4(DNM1):c.-15G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,468,936 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00059 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

DNM1
NM_004408.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.885

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 9-128203456-G-T is Benign according to our data. Variant chr9-128203456-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 384606.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-15G>T	5_prime_UTR	Exon 1 of 22	NP_004399.2	Q05193-1
DNM1	NM_001374269.1		c.-15G>T	5_prime_UTR	Exon 1 of 22	NP_001361198.1	A0A994J7J4
DNM1	NM_001288739.2		c.-15G>T	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.-15G>T	5_prime_UTR	Exon 1 of 22	ENSP00000362014.4	Q05193-1
DNM1	ENST00000486160.3	TSL:1	c.-15G>T	5_prime_UTR	Exon 1 of 22	ENSP00000420045.1	Q05193-2
DNM1	ENST00000341179.11	TSL:1	c.-15G>T	5_prime_UTR	Exon 1 of 23	ENSP00000345680.7	Q05193-3

Frequencies

GnomAD3 genomes

AF:

0.000594

AC:

AN:

151624

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000613

AC:

AN:

97850

AF XY:

0.0000535

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000463

AC:

AN:

1317204

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

649630

show subpopulations

African (AFR)

AF:

0.00193

AC:

AN:

26876

American (AMR)

AF:

0.00

AC:

AN:

25416

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22816

East Asian (EAS)

AF:

0.00

AC:

AN:

27974

South Asian (SAS)

AF:

0.00

AC:

AN:

72562

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41772

Middle Eastern (MID)

AF:

0.000400

AC:

AN:

5000

European-Non Finnish (NFE)

AF:

0.00000192

AC:

AN:

1041040

Other (OTH)

AF:

0.0000930

AC:

AN:

53748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000593

AC:

AN:

151732

Hom.:

Cov.:

AF XY:

0.000486

AC XY:

AN XY:

74148

show subpopulations

African (AFR)

AF:

0.00210

AC:

AN:

41516

American (AMR)

AF:

0.000197

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67792

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

Bravo

AF:

0.000597

ClinVar

ClinVar submissions

Significance:Likely 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

-0.50

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.89

PromoterAI

0.039

Neutral

(source)

Mutation Taster

=295/5

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