Variant 16-31722680-C-T 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.58C>T(p.His20Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KRBOX5
NM_001130913.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.79

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=0.12867379).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRBOX5	NM_001130913.2 linkuse as main transcript	c.58C>T	p.His20Tyr	missense_variant	2/5	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.58C>T	p.His20Tyr	missense_variant	2/5	1	NM_001130913.2	ENSP00000319222.9		Q7Z2F6-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461042

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726810

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000966

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

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

Apr 08, 2024

The c.58C>T (p.H20Y) alteration is located in exon 2 (coding exon 2) of the ZNF720 gene. This alteration results from a C to T substitution at nucleotide position 58, causing the histidine (H) at amino acid position 20 to be replaced by a tyrosine (Y). 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

0.064

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.64

CADD

Benign

4.1

DANN

Benign

0.87

DEOGEN2

Benign

0.0039

T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.11

T;T;T

M_CAP

Benign

0.0018

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.38

N;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

0.55

N;N;N

REVEL

Benign

0.027

Sift

Uncertain

0.011

D;D;D

Sift4G

Benign

0.090

T;T;T

Polyphen

0.012

B;.;.

Vest4

0.20

MutPred

0.54

Loss of disorder (P = 0.0377);.;Loss of disorder (P = 0.0377);

MVP

0.014

MPC

0.17

ClinPred

0.040

GERP RS

-1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.048

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