Variant chr16-31753778-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130913.2(KRBOX5):c.239A>G(p.His80Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000255 in 1,495,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

KRBOX5
NM_001130913.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.448

Variant links:

Genes affected

KRBOX5 (HGNC:26987): (KRAB box domain containing 5) Predicted to be involved in regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

KRBOX5 links:

KRBOX5 (HGNC:):

KRBOX5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08959943).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRBOX5	NM_001130913.2 linkuse as main transcript	c.239A>G	p.His80Arg	missense_variant	4/5	ENST00000316491.14	NP_001124385.1	Q7Z2F6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRBOX5	ENST00000316491.14 linkuse as main transcript	c.239A>G	p.His80Arg	missense_variant	4/5	1	NM_001130913.2	ENSP00000319222.9		Q7Z2F6-1

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

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:

0.000456

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000172

AC:

AN:

122174

Hom.:

AF XY:

0.000169

AC XY:

AN XY:

65016

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:

0.000413

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000259

AC:

348

AN:

1342906

Hom.:

Cov.:

AF XY:

0.000248

AC XY:

163

AN XY:

658148

show subpopulations

Gnomad4 AFR exome

AF:

0.0000347

Gnomad4 AMR exome

AF:

0.0000426

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000142

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000322

Gnomad4 OTH exome

AF:

0.000108

GnomAD4 genome

AF:

0.000223

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000723

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:

0.000456

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000298

Hom.:

Bravo

AF:

0.000151

ExAC

AF:

0.0000405

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

Nov 13, 2023

The c.239A>G (p.H80R) alteration is located in exon 4 (coding exon 4) of the ZNF720 gene. This alteration results from a A to G substitution at nucleotide position 239, causing the histidine (H) at amino acid position 80 to be replaced by an arginine (R). 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

0.071

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.39

CADD

Benign

6.4

DANN

Benign

0.86

DEOGEN2

Benign

0.085

.;T;.;.;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.44

T;T;T;T;T

M_CAP

Benign

0.0084

MetaRNN

Benign

0.090

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.8

.;L;.;.;.

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-6.7

D;D;D;D;D

REVEL

Benign

0.030

Sift

Pathogenic

0.0

D;D;T;D;D

Sift4G

Pathogenic

0.0

D;T;D;T;T

Polyphen

0.014, 0.96

.;B;D;.;.

Vest4

0.19

MVP

0.048

MPC

0.68

ClinPred

0.13

GERP RS

0.67

Varity_R

0.12

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