Variant 1-10639068-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001079843.3(CASZ1):c.5154C>A(p.Asp1718Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,129,118 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 3 hom. )

Consequence

CASZ1
NM_001079843.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.44

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0063269734).

BP6

Variant 1-10639068-G-T is Benign according to our data. Variant chr1-10639068-G-T is described in ClinVar as [Benign]. Clinvar id is 2160262.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASZ1	NM_001079843.3 linkuse as main transcript	c.5154C>A	p.Asp1718Glu	missense_variant	21/21	ENST00000377022.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASZ1	ENST00000377022.8 linkuse as main transcript	c.5154C>A	p.Asp1718Glu	missense_variant	21/21	1	NM_001079843.3	P1	Q86V15-1

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

146508

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00619

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000607

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000829

AC:

AN:

89258

Hom.:

AF XY:

0.000759

AC XY:

AN XY:

51352

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000809

Gnomad OTH exome

AF:

0.00128

GnomAD4 exome

AF:

0.000134

AC:

132

AN:

982610

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

474698

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00918

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000168

Gnomad4 OTH exome

AF:

0.000271

GnomAD4 genome

AF:

0.000177

AC:

AN:

146508

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

AN XY:

71244

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00619

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000607

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000158

Hom.:

Bravo

AF:

0.000246

ExAC

AF:

0.000364

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.14

Eigen

Benign

-0.087

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.55

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.0063

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.66

REVEL

Benign

0.083

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.060

Polyphen

0.75

Vest4

0.20

MutPred

0.12

Loss of glycosylation at S1722 (P = 0.25);

MVP

0.043

ClinPred

0.23

GERP RS

3.1

Varity_R

0.23

gMVP

0.031

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