19-12133310-G-C

Variant names:

Variant summary

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

The NM_021143.4(ZNF20):c.876C>G(p.Phe292Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000582 in 1,614,140 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: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

ZNF20
NM_021143.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.03

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:48368): (ZNF625-ZNF20 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring zinc finger protein 625 (ZNF625) and zinc finger protein 20 (ZNF20) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ZNF625-ZNF20 links:

ENSG00000290812 (HGNC:):

ENSG00000290812 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=0.028361976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF20	NM_021143.4 link	c.876C>G	p.Phe292Leu	missense_variant	Exon 4 of 4	ENST00000334213.10	NP_066966.2	P17024
ZNF20	NM_001203250.2 link	c.867C>G	p.Phe289Leu	missense_variant	Exon 4 of 4		NP_001190179.1
ZNF625-ZNF20	NR_037802.1 link	n.1458C>G		non_coding_transcript_exon_variant	Exon 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF20	ENST00000334213.10 link	c.876C>G	p.Phe292Leu	missense_variant	Exon 4 of 4	1	NM_021143.4	ENSP00000335437.5	P17024
ZNF625-ZNF20	ENST00000430024.5 link	n.*907C>G		non_coding_transcript_exon_variant	Exon 8 of 8	5		ENSP00000457423.1	F8WDT6
ZNF625-ZNF20	ENST00000430024.5 link	n.*907C>G		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000457423.1	F8WDT6

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000956

GnomAD3 exomes

AF:

0.0000758

AC:

AN:

250718

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.00101

Gnomad AMR exome

AF:

0.0000579

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:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.000179

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000322

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000196

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:

0.000946

Alfa

AF:

0.0000378

Hom.:

Bravo

AF:

0.000310

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.876C>G (p.F292L) alteration is located in exon 4 (coding exon 4) of the ZNF20 gene. This alteration results from a C to G substitution at nucleotide position 876, causing the phenylalanine (F) at amino acid position 292 to be replaced by a leucine (L). 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

0.98

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.00057

LIST_S2

Benign

0.68

M_CAP

Benign

0.0027

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.13

Sift

Uncertain

0.021

Sift4G

Uncertain

0.031

Polyphen

0.86

Vest4

0.15

MutPred

0.67

Gain of ubiquitination at K290 (P = 0.1204);

MVP

0.48

MPC

0.72

ClinPred

0.20

GERP RS

-1.4

Varity_R

0.23

gMVP

0.036

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