rs777721501

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021143.4(ZNF20):​c.1232G>T​(p.Arg411Leu) 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. 14/21 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. R411H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF20
NM_021143.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.12
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]
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]

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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=0.08479351).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF20NM_021143.4 linkc.1232G>T p.Arg411Leu missense_variant Exon 4 of 4 ENST00000334213.10 NP_066966.2 P17024
ZNF20NM_001203250.2 linkc.1223G>T p.Arg408Leu missense_variant Exon 4 of 4 NP_001190179.1
ZNF625-ZNF20NR_037802.1 linkn.1814G>T non_coding_transcript_exon_variant Exon 8 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF20ENST00000334213.10 linkc.1232G>T p.Arg411Leu missense_variant Exon 4 of 4 1 NM_021143.4 ENSP00000335437.5 P17024
ZNF625-ZNF20ENST00000430024.5 linkn.*1263G>T non_coding_transcript_exon_variant Exon 8 of 8 5 ENSP00000457423.1 F8WDT6
ZNF625-ZNF20ENST00000430024.5 linkn.*1263G>T 3_prime_UTR_variant Exon 8 of 8 5 ENSP00000457423.1 F8WDT6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.29
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
8.2
DANN
Benign
0.87
DEOGEN2
Benign
0.071
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.00020
N
LIST_S2
Benign
0.23
T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.085
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
-0.070
N
PrimateAI
Benign
0.21
T
PROVEAN
Pathogenic
-4.8
D
REVEL
Benign
0.058
Sift
Benign
0.049
D
Sift4G
Benign
0.14
T
Polyphen
0.21
B
Vest4
0.13
MutPred
0.54
Loss of MoRF binding (P = 0.0106);
MVP
0.21
MPC
0.23
ClinPred
0.18
T
GERP RS
-1.9
Varity_R
0.14
gMVP
0.033

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777721501; hg19: chr19-12243769; API