Variant chr19-53068426-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001322131.2(ZNF160):c.2108A>G(p.Lys703Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,614,060 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 4 hom. )

Consequence

ZNF160
NM_001322131.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0350

Variant links:

Genes affected

ZNF160 (HGNC:12948): (zinc finger protein 160) The protein encoded by this gene is a Kruppel-related zinc finger protein which is characterized by the presence of an N-terminal repressor domain, the Kruppel-associated box (KRAB). The KRAB domain is a potent repressor of transcription; thus this protein may function in transcription regulation. Multiple transcript variants have been found for this gene. [provided by RefSeq, Apr 2016]

ZNF160 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010578454).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF160	NM_001322131.2 linkuse as main transcript	c.2108A>G	p.Lys703Arg	missense_variant	6/6	ENST00000683776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF160	ENST00000683776.1 linkuse as main transcript	c.2108A>G	p.Lys703Arg	missense_variant	6/6		NM_001322131.2	P1	Q9HCG1-1

Frequencies

GnomAD3 genomes

AF:

0.000658

AC:

100

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00126

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000764

AC:

192

AN:

251394

Hom.:

AF XY:

0.000707

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00133

AC:

1943

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

896

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000374

Gnomad4 NFE exome

AF:

0.00162

Gnomad4 OTH exome

AF:

0.00108

GnomAD4 genome

AF:

0.000657

AC:

100

AN:

152200

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.000763

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000749

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00169

EpiControl

AF:

0.00136

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

Jun 21, 2021

The c.2108A>G (p.K703R) alteration is located in exon 7 (coding exon 4) of the ZNF160 gene. This alteration results from a A to G substitution at nucleotide position 2108, causing the lysine (K) at amino acid position 703 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

0.21

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T;T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.0023

LIST_S2

Uncertain

0.89

.;.;D;D

M_CAP

Benign

0.0026

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.4

.;N;N;.

REVEL

Benign

0.058

Sift

Benign

0.043

.;D;D;.

Sift4G

Uncertain

0.057

T;T;T;T

Polyphen

0.92

P;P;P;.

Vest4

0.11

MVP

0.12

MPC

0.70

ClinPred

0.054

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.075

gMVP

0.029

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