Variant chr19-53068811-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001322131.2(ZNF160):c.1723G>A(p.Ala575Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000707 in 1,612,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

ZNF160
NM_001322131.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.50

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014510989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF160	NM_001322131.2 linkuse as main transcript	c.1723G>A	p.Ala575Thr	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.1723G>A	p.Ala575Thr	missense_variant	6/6		NM_001322131.2	P1	Q9HCG1-1

Frequencies

GnomAD3 genomes

AF:

0.000258

AC:

AN:

151434

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000850

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000836

AC:

AN:

251304

Hom.:

AF XY:

0.0000810

AC XY:

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000507

AC:

AN:

1460494

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

726572

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000264

AC:

AN:

151554

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

74074

show subpopulations

Gnomad4 AFR

AF:

0.000872

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000988

Hom.:

Bravo

AF:

0.000280

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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 07, 2024

The c.1723G>A (p.A575T) alteration is located in exon 7 (coding exon 4) of the ZNF160 gene. This alteration results from a G to A substitution at nucleotide position 1723, causing the alanine (A) at amino acid position 575 to be replaced by a threonine (T). 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

0.14

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.40

DANN

Benign

0.16

DEOGEN2

Benign

0.0057

T;T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00011

LIST_S2

Uncertain

0.88

.;.;D;D

M_CAP

Benign

0.0014

MetaRNN

Benign

0.015

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.075

N;N;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

0.30

.;N;N;.

REVEL

Benign

0.0060

Sift

Benign

0.49

.;T;T;.

Sift4G

Benign

0.57

T;T;T;T

Polyphen

0.21

B;B;B;.

Vest4

0.039

MVP

0.040

MPC

0.25

ClinPred

0.0061

GERP RS

-0.013

Varity_R

0.016

gMVP

0.035

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