rs142432944

Variant names:

• chr9-128203587-C-T
• rs142432944
• NM_004408.4:c.117C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-128203587-C-T
• chr9-128203587-C-A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_004408.4(DNM1):​c.117C>T​(p.Gly39Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,551,794 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 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: DNM1 NM_004408.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.251
• Publications: 1 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 9-128203587-C-T is Benign according to our data. Variant chr9-128203587-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 391413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.251 with no splicing effect.

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.117C>T	p.Gly39Gly	synonymous	Exon 1 of 22	NP_004399.2	Q05193-1
	DNM1	NM_001374269.1		c.117C>T	p.Gly39Gly	synonymous	Exon 1 of 22	NP_001361198.1	A0A994J7J4
	DNM1	NM_001288739.2		c.117C>T	p.Gly39Gly	synonymous	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.117C>T	p.Gly39Gly	synonymous	Exon 1 of 22	ENSP00000362014.4	Q05193-1
	DNM1	ENST00000486160.3	TSL:1	c.117C>T	p.Gly39Gly	synonymous	Exon 1 of 22	ENSP00000420045.1	Q05193-2
	DNM1	ENST00000634267.2	TSL:5	c.117C>T	p.Gly39Gly	synonymous	Exon 1 of 22	ENSP00000489096.1	A0A0U1RQP1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 151916 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000113 AC: 21 AN: 186040 AF XY: 0.0000671

Gnomad AFR exome AF: 0.000221

Gnomad AMR exome AF: 0.0000371

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000234 AC: 328 AN: 1399878 Hom.: 1 Cov.: 30 AF XY: 0.000215 AC XY: 150 AN XY: 696420

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28896

American (AMR) AF: 0.0000535 AC: 2 AN: 37412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24350

East Asian (EAS) AF: 0.00 AC: 0 AN: 32240

South Asian (SAS) AF: 0.00 AC: 0 AN: 80482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5324

European-Non Finnish (NFE) AF: 0.000290 AC: 315 AN: 1085322

Other (OTH) AF: 0.000191 AC: 11 AN: 57558

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000724 AC: 11 AN: 151916 Hom.: 0 Cov.: 32 AF XY: 0.0000674 AC XY: 5 AN XY: 74202

African (AFR) AF: 0.0000241 AC: 1 AN: 41408

American (AMR) AF: 0.0000655 AC: 1 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67940

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000131 Hom.: 0

Bravo AF: 0.0000982

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Developmental and epileptic encephalopathy, 31A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.97
PhyloP100		0.25
PromoterAI		-0.050	Neutral

Splicing

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

Other links and lift over

dbSNP: rs142432944; hg19: chr9-130965866;