1-10639098-CTCGTCGTCGTCCTCG-C

Position:

• chr1-10639098-CTCGTCGTCGTCCTCG-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001079843.3(CASZ1):​c.5109_5123del​(p.Asp1703_Asp1707del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0014 in 1,119,682 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (2 hom.)
• Consequence: CASZ1 NM_001079843.3 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

Genes affected

CASZ1 (HGNC:26002): (castor zinc finger 1) The protein encoded by this gene is a zinc finger transcription factor. The encoded protein may function as a tumor suppressor, and single nucleotide polymorphisms in this gene are associated with blood pressure variation. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 270 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASZ1	NM_001079843.3	c.5109_5123del	p.Asp1703_Asp1707del	inframe_deletion	21/21	ENST00000377022.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASZ1	ENST00000377022.8	c.5109_5123del	p.Asp1703_Asp1707del	inframe_deletion	21/21	1	NM_001079843.3	P1

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 269 AN: 143630 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00444

Gnomad SAS AF: 0.000652

Gnomad FIN AF: 0.000119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00136

Gnomad OTH AF: 0.000510

GnomAD3 exomes AF: 0.000401 AC: 38 AN: 94776 Hom.: 0 AF XY: 0.000422 AC XY: 23 AN XY: 54526

Gnomad AFR exome AF: 0.000828

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00176

Gnomad SAS exome AF: 0.000125

Gnomad FIN exome AF: 0.000203

Gnomad NFE exome AF: 0.000612

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00133 AC: 1297 AN: 976022 Hom.: 2 AF XY: 0.00127 AC XY: 602 AN XY: 474320

Gnomad4 AFR exome AF: 0.00255

Gnomad4 AMR exome AF: 0.000461

Gnomad4 ASJ exome AF: 0.000163

Gnomad4 EAS exome AF: 0.00457

Gnomad4 SAS exome AF: 0.000455

Gnomad4 FIN exome AF: 0.000313

Gnomad4 NFE exome AF: 0.00135

Gnomad4 OTH exome AF: 0.00159

GnomAD4 genome AF: 0.00188 AC: 270 AN: 143660 Hom.: 0 Cov.: 32 AF XY: 0.00187 AC XY: 131 AN XY: 69898

Gnomad4 AFR AF: 0.00341

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00446

Gnomad4 SAS AF: 0.000653

Gnomad4 FIN AF: 0.000119

Gnomad4 NFE AF: 0.00136

Gnomad4 OTH AF: 0.000506

Alfa AF: 0.000254 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Dec 13, 2023

This variant, c.5109_5123del, results in the deletion of 5 amino acid(s) of the CASZ1 protein (p.Asp1703_Asp1707del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CASZ1-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs762322588; hg19: chr1-10699155;