Variant chr1-71066833-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_203350.3(ZRANB2):c.872G>T(p.Arg291Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,126 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZRANB2
NM_203350.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRANB2	NM_203350.3 linkuse as main transcript	c.872G>T	p.Arg291Ile	missense_variant	9/10	ENST00000370920.8	NP_976225.1	O95218-1
ZRANB2	NM_005455.5 linkuse as main transcript	c.872G>T	p.Arg291Ile	missense_variant	9/11		NP_005446.2	O95218-2
ZRANB2	XM_047434733.1 linkuse as main transcript	c.872G>T	p.Arg291Ile	missense_variant	9/10		XP_047290689.1
ZRANB2-AS1	NR_038420.1 linkuse as main transcript	n.1327C>A		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.872G>T	p.Arg291Ile	missense_variant	9/10	1	NM_203350.3	ENSP00000359958.3		O95218-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249796

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135020

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460126

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726154

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Jan 25, 2023

The c.872G>T (p.R291I) alteration is located in exon 9 (coding exon 9) of the ZRANB2 gene. This alteration results from a G to T substitution at nucleotide position 872, causing the arginine (R) at amino acid position 291 to be replaced by an isoleucine (I). 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

Uncertain

0.36

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.40

T;.;.

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;.;D

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.47

T;T;T

MetaSVM

Benign

-0.29

MutationAssessor

Uncertain

2.6

M;M;M

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.5

N;N;.

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

D;D;.

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.53

MutPred

0.32

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);

MVP

0.45

MPC

0.23

ClinPred

0.78

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.54

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