Variant chr19-53068089-T-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_001322131.2(ZNF160):c.2445A>C(p.Lys815Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF160
NM_001322131.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.24

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:

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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=0.1848009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF160	NM_001322131.2 linkuse as main transcript	c.2445A>C	p.Lys815Asn	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.2445A>C	p.Lys815Asn	missense_variant	6/6		NM_001322131.2	P1	Q9HCG1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243380

Hom.:

AF XY:

0.00000763

AC XY:

AN XY:

131144

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:

0.00000909

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452084

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721398

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000378

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

Feb 10, 2023

The c.2445A>C (p.K815N) alteration is located in exon 7 (coding exon 4) of the ZNF160 gene. This alteration results from a A to C substitution at nucleotide position 2445, causing the lysine (K) at amino acid position 815 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

Pathogenic

0.61

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.00064

LIST_S2

Benign

0.46

.;.;T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.18

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;M;M;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-3.3

.;D;D;.

REVEL

Benign

0.097

Sift

Pathogenic

0.0

.;D;D;.

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

0.95

P;P;P;.

Vest4

0.16

MutPred

0.49

Loss of methylation at K815 (P = 0.0017);Loss of methylation at K815 (P = 0.0017);Loss of methylation at K815 (P = 0.0017);.;

MVP

0.43

MPC

0.48

ClinPred

0.68

GERP RS

-1.2

Varity_R

0.29

gMVP

0.018

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

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