Variant 1-10639058-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001079843.3(CASZ1):c.5164T>C(p.Ser1722Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000831 in 1,083,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

CASZ1
NM_001079843.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.80

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24554509).

BS2

High AC in GnomAdExome4 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.5164T>C	p.Ser1722Pro	missense_variant	21/21	ENST00000377022.8	NP_001073312.1	Q86V15-1B3KRV8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASZ1	ENST00000377022.8 linkuse as main transcript	c.5164T>C	p.Ser1722Pro	missense_variant	21/21	1	NM_001079843.3	ENSP00000366221.3		Q86V15-1

Frequencies

GnomAD3 genomes

AF:

0.0000210

AC:

AN:

143000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000762

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000638

AC:

AN:

940132

Hom.:

Cov.:

AF XY:

0.00000891

AC XY:

AN XY:

449140

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000616

Gnomad4 OTH exome

AF:

0.0000317

GnomAD4 genome

AF:

0.0000210

AC:

AN:

143000

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

69456

show subpopulations

Gnomad4 AFR

AF:

0.0000762

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.5164T>C (p.S1722P) alteration is located in exon 21 (coding exon 18) of the CASZ1 gene. This alteration results from a T to C substitution at nucleotide position 5164, causing the serine (S) at amino acid position 1722 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.14

Eigen

Benign

0.0025

Eigen_PC

Benign

-0.075

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.55

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.77

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.016

Polyphen

0.98

Vest4

0.29

MutPred

0.063

Loss of phosphorylation at S1722 (P = 0.0038);

MVP

0.043

ClinPred

0.69

GERP RS

2.5

Varity_R

0.32

gMVP

0.049

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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