9-128192366-CAAAAA-CAAAAAAA

Variant names:

• chr9-128192366-C-CAA
• rs57931082
• ENST00000866501.1:c.-519_-518dupTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_012127.3(CIZ1):​c.-5-1506_-5-1505dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.029 (104 hom., cov: 0)
• Consequence: CIZ1 NM_012127.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.202
• Publications: 0 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AR, AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 31A

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• developmental and epileptic encephalopathy, 31B

  Inheritance: AR, AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Lennox-Gastaut syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0795 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012127.3. 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
	CIZ1	NM_012127.3		c.-5-1506_-5-1505dupTT		intron	N/A	NP_036259.2
	CIZ1	NM_001131015.2		c.-5-1506_-5-1505dupTT		intron	N/A	NP_001124487.1	Q9ULV3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIZ1	ENST00000866501.1		c.-519_-518dupTT		5_prime_UTR	Exon 1 of 17	ENSP00000536560.1
	CIZ1	ENST00000866502.1		c.-642_-641dupTT		5_prime_UTR	Exon 1 of 16	ENSP00000536561.1
	CIZ1	ENST00000866503.1		c.-519_-518dupTT		5_prime_UTR	Exon 1 of 16	ENSP00000536562.1

Frequencies

GnomAD3 genomes AF: 0.0294 AC: 4092 AN: 139356 Hom.: 102 Cov.: 0

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.0336

Gnomad EAS AF: 0.0145

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.0779

Gnomad NFE AF: 0.0289

Gnomad OTH AF: 0.0395

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0294 AC: 4099 AN: 139372 Hom.: 104 Cov.: 0 AF XY: 0.0300 AC XY: 2015 AN XY: 67102

African (AFR) AF: 0.0102 AC: 383 AN: 37558

American (AMR) AF: 0.0835 AC: 1172 AN: 14038

Ashkenazi Jewish (ASJ) AF: 0.0336 AC: 114 AN: 3390

East Asian (EAS) AF: 0.0146 AC: 69 AN: 4730

South Asian (SAS) AF: 0.0154 AC: 65 AN: 4218

European-Finnish (FIN) AF: 0.0224 AC: 167 AN: 7454

Middle Eastern (MID) AF: 0.0810 AC: 23 AN: 284

European-Non Finnish (NFE) AF: 0.0289 AC: 1878 AN: 64892

Other (OTH) AF: 0.0402 AC: 77 AN: 1914

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs57931082; hg19: chr9-130954645;