Variant 1-71066839-C-T 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_203350.3(ZRANB2):c.866G>A(p.Arg289His) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,612,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ZRANB2
NM_203350.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85

Variant links:

Genes affected

ZRANB2 (HGNC:13058): (zinc finger RANBP2-type containing 2) Enables RNA binding activity. Predicted to be involved in RNA splicing and mRNA processing. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZRANB2 links:

ZRANB2-AS1 (HGNC:):

ZRANB2-AS1 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=0.13094297).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRANB2	NM_203350.3 linkuse as main transcript	c.866G>A	p.Arg289His	missense_variant	9/10	ENST00000370920.8	NP_976225.1	O95218-1
ZRANB2	NM_005455.5 linkuse as main transcript	c.866G>A	p.Arg289His	missense_variant	9/11		NP_005446.2	O95218-2
ZRANB2	XM_047434733.1 linkuse as main transcript	c.866G>A	p.Arg289His	missense_variant	9/10		XP_047290689.1
ZRANB2-AS1	NR_038420.1 linkuse as main transcript	n.1333C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRANB2	ENST00000370920.8 linkuse as main transcript	c.866G>A	p.Arg289His	missense_variant	9/10	1	NM_203350.3	ENSP00000359958.3		O95218-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000440

AC:

AN:

249884

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

135056

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1460168

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

726202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000468

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000741

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

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

Mar 24, 2023

The c.866G>A (p.R289H) alteration is located in exon 9 (coding exon 9) of the ZRANB2 gene. This alteration results from a G to A substitution at nucleotide position 866, causing the arginine (R) at amino acid position 289 to be replaced by a histidine (H). 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

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;.;.

Eigen

Benign

0.095

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.79

T;.;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.5

M;M;M

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.1

N;N;.

REVEL

Benign

0.072

Sift

Pathogenic

0.0

D;D;.

Sift4G

Uncertain

0.020

D;D;D

Polyphen

0.0010

B;B;B

Vest4

0.41

MVP

0.33

MPC

0.16

ClinPred

0.20

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.51

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