Variant 1-10639086-G-GTCGTCGTCGTCC details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000377022.8(CASZ1):c.5135_5136insGGACGACGACGA(p.Glu1708_Asp1711dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000591 in 1,048,786 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000061 ( 1 hom. )

Consequence

CASZ1
ENST00000377022.8 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.06

Variant links:

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]

CASZ1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASZ1	NM_001079843.3 linkuse as main transcript	c.5135_5136insGGACGACGACGA	p.Glu1708_Asp1711dup	inframe_insertion	21/21	ENST00000377022.8	NP_001073312.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASZ1	ENST00000377022.8 linkuse as main transcript	c.5135_5136insGGACGACGACGA	p.Glu1708_Asp1711dup	inframe_insertion	21/21	1	NM_001079843.3	ENSP00000366221	P1	Q86V15-1

Frequencies

GnomAD3 genomes

AF:

0.0000453

AC:

AN:

132578

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000801

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000163

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000187

AC:

AN:

91066

Hom.:

AF XY:

0.000210

AC XY:

AN XY:

52464

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000908

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000769

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000611

AC:

AN:

916208

Hom.:

Cov.:

AF XY:

0.0000767

AC XY:

AN XY:

443496

show subpopulations

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:

0.00129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000641

Gnomad4 OTH exome

AF:

0.0000985

GnomAD4 genome

AF:

0.0000453

AC:

AN:

132578

Hom.:

Cov.:

AF XY:

0.0000620

AC XY:

AN XY:

64546

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000801

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000163

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 08, 2023

This variant, c.5124_5135dup, results in the insertion of 4 amino acid(s) of the CASZ1 protein (p.Glu1708_Asp1711dup), 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. 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

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over