NM_004408.4:c.-27T>G

Variant names:

• chr9-128203444-T-G
• rs373766853
• NM_004408.4:c.-27T>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_004408.4(DNM1):​c.-27T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000408 in 1,445,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (0 hom.)
• Consequence: DNM1 NM_004408.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.290
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-128203444-T-G is Benign according to our data. Variant chr9-128203444-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 512176.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM1	NM_004408.4	MANE Select	c.-27T>G		5_prime_UTR	Exon 1 of 22	NP_004399.2	Q05193-1
	DNM1	NM_001374269.1		c.-27T>G		5_prime_UTR	Exon 1 of 22	NP_001361198.1	A0A994J7J4
	DNM1	NM_001288739.2		c.-27T>G		5_prime_UTR	Exon 1 of 22	NP_001275668.1	Q05193-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM1	ENST00000372923.8	TSL:1 MANE Select	c.-27T>G		5_prime_UTR	Exon 1 of 22	ENSP00000362014.4	Q05193-1
	DNM1	ENST00000486160.3	TSL:1	c.-27T>G		5_prime_UTR	Exon 1 of 22	ENSP00000420045.1	Q05193-2
	DNM1	ENST00000341179.11	TSL:1	c.-27T>G		5_prime_UTR	Exon 1 of 23	ENSP00000345680.7	Q05193-3

Frequencies

GnomAD3 genomes AF: 0.000403 AC: 61 AN: 151414 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000579

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000192

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000738

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000332 AC: 27 AN: 81294 AF XY: 0.000340

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000782

Gnomad ASJ exome AF: 0.000464

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000735

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000408 AC: 528 AN: 1293522 Hom.: 0 Cov.: 30 AF XY: 0.000396 AC XY: 252 AN XY: 636460

African (AFR) AF: 0.0000382 AC: 1 AN: 26168

American (AMR) AF: 0.0000874 AC: 2 AN: 22896

Ashkenazi Jewish (ASJ) AF: 0.000763 AC: 17 AN: 22278

East Asian (EAS) AF: 0.00 AC: 0 AN: 27170

South Asian (SAS) AF: 0.00 AC: 0 AN: 70384

European-Finnish (FIN) AF: 0.0000254 AC: 1 AN: 39400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4418

European-Non Finnish (NFE) AF: 0.000479 AC: 492 AN: 1028198

Other (OTH) AF: 0.000285 AC: 15 AN: 52610

GnomAD4 genome AF: 0.000403 AC: 61 AN: 151522 Hom.: 0 Cov.: 32 AF XY: 0.000324 AC XY: 24 AN XY: 74050

African (AFR) AF: 0.0000723 AC: 3 AN: 41470

American (AMR) AF: 0.000131 AC: 2 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.000579 AC: 2 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000192 AC: 2 AN: 10400

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000739 AC: 50 AN: 67702

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.000476 Hom.: 0

Bravo AF: 0.000416

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	16
DANN	Benign	0.73
PhyloP100		-0.29
PromoterAI		-0.083	Neutral
Mutation Taster		=299/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs373766853; hg19: chr9-130965723;