NM_001257975.2:c.45G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001257975.2(CIZ1):​c.45G>C​(p.Ala15Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000773 in 1,293,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A15A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: CIZ1 NM_001257975.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=1.32 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIZ1	NM_001257975.2	c.45G>C	p.Ala15Ala	synonymous_variant	Exon 1 of 18		NP_001244904.1
CIZ1	NM_012127.3	c.-5-1033G>C		intron_variant	Intron 1 of 16		NP_036259.2
CIZ1	NM_001131015.2	c.-5-1033G>C		intron_variant	Intron 1 of 17		NP_001124487.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIZ1	ENST00000538431.5	c.45G>C	p.Ala15Ala	synonymous_variant	Exon 1 of 18	2		ENSP00000439244.2
CIZ1	ENST00000634901.1	c.-5-1033G>C		intron_variant	Intron 4 of 19	5		ENSP00000489425.1
CIZ1	ENST00000372948.7	c.-5-1033G>C		intron_variant	Intron 1 of 17	2		ENSP00000362039.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.73e-7 AC: 1 AN: 1293550 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 635980

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000142

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.77

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-130954174;