Variant chr1-71065109-G-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.958C>A(p.His320Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,611,614 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H320L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 1 hom. )

Consequence

ZRANB2
NM_203350.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.07

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 (HGNC:):

ZRANB2 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=0.07685745).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRANB2	NM_203350.3 linkuse as main transcript	c.958C>A	p.His320Asn	missense_variant	10/10	ENST00000370920.8	NP_976225.1	O95218-1
ZRANB2	NM_005455.5 linkuse as main transcript	c.*70C>A		3_prime_UTR_variant	11/11		NP_005446.2	O95218-2
ZRANB2	XM_047434733.1 linkuse as main transcript	c.*610C>A		3_prime_UTR_variant	10/10		XP_047290689.1
ZRANB2-AS1	NR_038420.1 linkuse as main transcript	n.1260-1657G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRANB2	ENST00000370920.8 linkuse as main transcript	c.958C>A	p.His320Asn	missense_variant	10/10	1	NM_203350.3	ENSP00000359958.3		O95218-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000394

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

GnomAD3 exomes

AF:

0.0000684

AC:

AN:

248566

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

134578

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000467

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:

0.00000896

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1459556

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

726066

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000561

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000393

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:

0.0000718

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

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

Jul 02, 2024

The c.958C>A (p.H320N) alteration is located in exon 10 (coding exon 10) of the ZRANB2 gene. This alteration results from a C to A substitution at nucleotide position 958, causing the histidine (H) at amino acid position 320 to be replaced by an asparagine (N). 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

0.090

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.065

Eigen

Benign

-0.14

Eigen_PC

Benign

0.071

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.49

M_CAP

Benign

0.011

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.85

REVEL

Benign

0.039

Sift

Uncertain

0.019

Sift4G

Uncertain

0.028

Polyphen

0.0020

Vest4

0.37

MVP

0.30

MPC

0.14

ClinPred

0.11

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.31

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