Genetic Variant ZNF20:p.Arg238Pro (chr19-12133473-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021143.4(ZNF20):c.713G>C(p.Arg238Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R238H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF20
NM_021143.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.22

Publications

3 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1487037).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021143.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF20	NM_021143.4	MANE Select	c.713G>C	p.Arg238Pro	missense	Exon 4 of 4	NP_066966.2	P17024
ZNF20	NM_001203250.2		c.704G>C	p.Arg235Pro	missense	Exon 4 of 4	NP_001190179.1
ZNF625-ZNF20	NR_037802.1		n.1295G>C		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF20	ENST00000334213.10	TSL:1 MANE Select	c.713G>C	p.Arg238Pro	missense	Exon 4 of 4	ENSP00000335437.5	P17024
ZNF625-ZNF20	ENST00000430024.5	TSL:5	n.*744G>C		non_coding_transcript_exon	Exon 8 of 8	ENSP00000457423.1	F8WDT6
ZNF625-ZNF20	ENST00000430024.5	TSL:5	n.*744G>C		3_prime_UTR	Exon 8 of 8	ENSP00000457423.1	F8WDT6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.2

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.055

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00013

LIST_S2

Benign

0.16

M_CAP

Benign

0.0023

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

-3.2

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.1

REVEL

Benign

0.080

Sift

Benign

0.18

Sift4G

Benign

0.20

Polyphen

0.93

Vest4

0.15

MutPred

0.47

Loss of MoRF binding (P = 0.01)

MVP

0.35

MPC

0.53

ClinPred

0.31

GERP RS

-1.9

Varity_R

0.088

gMVP

0.094

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over