rs144814370

Variant names:

• chr9-128191895-C-A
• rs144814370
• NM_001257975.2:c.45G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-128191895-C-A
• chr9-128191895-C-G
• chr9-128191895-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001257975.2(CIZ1):​c.45G>T​(p.Ala15Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 1,445,730 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0036 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0046 (15 hom.)
• Consequence: CIZ1 NM_001257975.2 synonymous
• Clinical Significance: Benign/Likely benign no assertion criteria provided B:3
• Conservation: PhyloP100: 1.32
• 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: AD, AR Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 31A

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

  Inheritance: AD, AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 9-128191895-C-A is Benign according to our data. Variant chr9-128191895-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1174752.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.32 with no splicing effect.
• BS2: High AC in GnomAd4 at 553 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257975.2. 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_001257975.2		c.45G>T	p.Ala15Ala	synonymous	Exon 1 of 18	NP_001244904.1	F5H2X7
	CIZ1	NM_012127.3		c.-5-1033G>T		intron	N/A	NP_036259.2
	CIZ1	NM_001131015.2		c.-5-1033G>T		intron	N/A	NP_001124487.1	Q9ULV3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIZ1	ENST00000538431.5	TSL:2	c.45G>T	p.Ala15Ala	synonymous	Exon 1 of 18	ENSP00000439244.2	F5H2X7
	CIZ1	ENST00000866501.1		c.-46G>T		5_prime_UTR	Exon 1 of 17	ENSP00000536560.1
	CIZ1	ENST00000866502.1		c.-169G>T		5_prime_UTR	Exon 1 of 16	ENSP00000536561.1

Frequencies

GnomAD3 genomes AF: 0.00364 AC: 553 AN: 152072 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0128

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00516

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00250 AC: 178 AN: 71106 AF XY: 0.00257

Gnomad AFR exome AF: 0.000705

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0164

Gnomad NFE exome AF: 0.00409

Gnomad OTH exome AF: 0.000949

GnomAD4 exome AF: 0.00458 AC: 5927 AN: 1293540 Hom.: 15 Cov.: 31 AF XY: 0.00432 AC XY: 2745 AN XY: 635972

African (AFR) AF: 0.000708 AC: 19 AN: 26852

American (AMR) AF: 0.000774 AC: 20 AN: 25850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22494

East Asian (EAS) AF: 0.00 AC: 0 AN: 28896

South Asian (SAS) AF: 0.000199 AC: 14 AN: 70332

European-Finnish (FIN) AF: 0.0127 AC: 401 AN: 31530

Middle Eastern (MID) AF: 0.000560 AC: 3 AN: 5356

European-Non Finnish (NFE) AF: 0.00510 AC: 5253 AN: 1029126

Other (OTH) AF: 0.00409 AC: 217 AN: 53104

GnomAD4 genome AF: 0.00363 AC: 553 AN: 152190 Hom.: 3 Cov.: 31 AF XY: 0.00378 AC XY: 281 AN XY: 74412

African (AFR) AF: 0.00106 AC: 44 AN: 41538

American (AMR) AF: 0.00105 AC: 16 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0128 AC: 136 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00516 AC: 351 AN: 67974

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00159 Hom.: 0

Bravo AF: 0.00284

Asia WGS AF: 0.000578 AC: 2 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CIZ1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.92
PhyloP100		1.3
PromoterAI		0.049	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs144814370; hg19: chr9-130954174;