Genetic Variant NM_021143.4:c.887G>A (chr19-12133299-C-T) – 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.887G>A(p.Ser296Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF20
NM_021143.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.15

Publications

0 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:

Genome browser will be placed here

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=0.09711152).

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.887G>A	p.Ser296Asn	missense	Exon 4 of 4	NP_066966.2	P17024
ZNF20	NM_001203250.2		c.878G>A	p.Ser293Asn	missense	Exon 4 of 4	NP_001190179.1
ZNF625-ZNF20	NR_037802.1		n.1469G>A		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.887G>A	p.Ser296Asn	missense	Exon 4 of 4	ENSP00000335437.5	P17024
ZNF625-ZNF20	ENST00000430024.5	TSL:5	n.*918G>A		non_coding_transcript_exon	Exon 8 of 8	ENSP00000457423.1	F8WDT6
ZNF625-ZNF20	ENST00000430024.5	TSL:5	n.*918G>A		3_prime_UTR	Exon 8 of 8	ENSP00000457423.1	F8WDT6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.26

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.055

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.000040

LIST_S2

Benign

0.000083

M_CAP

Benign

0.0012

MetaRNN

Benign

0.097

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.2

PhyloP100

-1.1

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.3

REVEL

Benign

0.044

Sift

Benign

0.18

Sift4G

Benign

0.075

Polyphen

0.013

Vest4

0.091

MutPred

0.64

Loss of disorder (P = 0.0538)

MVP

0.32

MPC

0.17

ClinPred

0.063

GERP RS

1.1

Varity_R

0.048

gMVP

0.0070

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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