Variant chr19-12133090-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000334213.10(ZNF20):c.1096C>T(p.Pro366Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF20
ENST00000334213.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.52

Variant links:

Genes affected

ZNF20 (HGNC:12992): (zinc finger protein 20) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF20 links:

ZNF625-ZNF20 (HGNC:):

ZNF625-ZNF20 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3855366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF20	NM_021143.4 linkuse as main transcript	c.1096C>T	p.Pro366Ser	missense_variant	4/4	ENST00000334213.10	NP_066966.2
ZNF625-ZNF20	NR_037802.1 linkuse as main transcript	n.1678C>T		non_coding_transcript_exon_variant	8/8
ZNF20	NM_001203250.2 linkuse as main transcript	c.1087C>T	p.Pro363Ser	missense_variant	4/4		NP_001190179.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF20	ENST00000334213.10 linkuse as main transcript	c.1096C>T	p.Pro366Ser	missense_variant	4/4	1	NM_021143.4	ENSP00000335437	P1
	ENST00000601686.1 linkuse as main transcript	n.165-2685G>A		intron_variant, non_coding_transcript_variant		4
ZNF20	ENST00000600335.5 linkuse as main transcript	c.191+2410C>T		intron_variant		4		ENSP00000470025
ZNF20	ENST00000480770.5 linkuse as main transcript	n.222-2391C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

1461858

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151994

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74230

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

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 01, 2022

The c.1096C>T (p.P366S) alteration is located in exon 4 (coding exon 4) of the ZNF20 gene. This alteration results from a C to T substitution at nucleotide position 1096, causing the proline (P) at amino acid position 366 to be replaced by a serine (S). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Benign

-0.085

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.46

M_CAP

Benign

0.0045

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.3

MutationTaster

Benign

0.74

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-7.3

REVEL

Benign

0.083

Sift

Uncertain

0.028

Sift4G

Uncertain

0.017

Polyphen

1.0

Vest4

0.21

MVP

0.51

MPC

0.55

ClinPred

0.96

GERP RS

0.94

Varity_R

0.21

gMVP

0.024

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