19-12133023-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The ENST00000334213.10(ZNF20):​c.1163C>T​(p.Thr388Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,613,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

ZNF20
ENST00000334213.10 missense

Scores

1
18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.844
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]

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=0.071847916).
BP6
Variant 19-12133023-G-A is Benign according to our data. Variant chr19-12133023-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2389114.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF20NM_021143.4 linkuse as main transcriptc.1163C>T p.Thr388Met missense_variant 4/4 ENST00000334213.10 NP_066966.2
ZNF625-ZNF20NR_037802.1 linkuse as main transcriptn.1745C>T non_coding_transcript_exon_variant 8/8
ZNF20NM_001203250.2 linkuse as main transcriptc.1154C>T p.Thr385Met missense_variant 4/4 NP_001190179.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF20ENST00000334213.10 linkuse as main transcriptc.1163C>T p.Thr388Met missense_variant 4/41 NM_021143.4 ENSP00000335437 P1
ENST00000601686.1 linkuse as main transcriptn.165-2752G>A intron_variant, non_coding_transcript_variant 4
ZNF20ENST00000600335.5 linkuse as main transcriptc.191+2477C>T intron_variant 4 ENSP00000470025
ZNF20ENST00000480770.5 linkuse as main transcriptn.222-2324C>T intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152052
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000435
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:
0.000189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000760
AC:
19
AN:
250158
Hom.:
0
AF XY:
0.0000516
AC XY:
7
AN XY:
135632
show subpopulations
Gnomad AFR exome
AF:
0.0000643
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.000124
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000179
AC:
261
AN:
1461772
Hom.:
0
Cov.:
31
AF XY:
0.000162
AC XY:
118
AN XY:
727164
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.000318
Gnomad4 NFE exome
AF:
0.000197
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152052
Hom.:
0
Cov.:
33
AF XY:
0.000175
AC XY:
13
AN XY:
74270
show subpopulations
Gnomad4 AFR
AF:
0.000435
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000200
Hom.:
0
Bravo
AF:
0.000212
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.000459
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000742
AC:
9
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsMay 27, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
10
DANN
Benign
0.74
DEOGEN2
Benign
0.16
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.000090
N
LIST_S2
Benign
0.084
T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.072
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.029
Sift
Benign
0.096
T
Sift4G
Benign
0.15
T
Polyphen
0.17
B
Vest4
0.043
MVP
0.24
MPC
0.20
ClinPred
0.027
T
GERP RS
-1.9
Varity_R
0.028
gMVP
0.026

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.

Other links and lift over

dbSNP: rs199910328; hg19: chr19-12243838; API