19-36719332-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001322917.1(ZNF567):​c.608C>T​(p.Thr203Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,612,484 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 1 hom. )

Consequence

ZNF567
NM_001322917.1 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.43
Variant links:
Genes affected
ZNF567 (HGNC:28696): (zinc finger protein 567) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
ZNF850 (HGNC:27994): (zinc finger protein 850) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active 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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.011468172).
BP6
Variant 19-36719332-C-T is Benign according to our data. Variant chr19-36719332-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2402438.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF567NM_001322917.1 linkc.608C>T p.Thr203Met missense_variant Exon 6 of 6 ENST00000682579.1 NP_001309846.1 Q8N184-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF567ENST00000682579.1 linkc.608C>T p.Thr203Met missense_variant Exon 6 of 6 NM_001322917.1 ENSP00000507048.1 Q8N184-3

Frequencies

GnomAD3 genomes
AF:
0.000197
AC:
30
AN:
151982
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000363
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000623
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000218
AC:
54
AN:
248130
Hom.:
0
AF XY:
0.000208
AC XY:
28
AN XY:
134412
show subpopulations
Gnomad AFR exome
AF:
0.000881
Gnomad AMR exome
AF:
0.000117
Gnomad ASJ exome
AF:
0.00211
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000366
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000178
Gnomad OTH exome
AF:
0.000334
GnomAD4 exome
AF:
0.0000986
AC:
144
AN:
1460384
Hom.:
1
Cov.:
33
AF XY:
0.000123
AC XY:
89
AN XY:
726422
show subpopulations
Gnomad4 AFR exome
AF:
0.000659
Gnomad4 AMR exome
AF:
0.0000903
Gnomad4 ASJ exome
AF:
0.00161
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000431
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.000265
GnomAD4 genome
AF:
0.000197
AC:
30
AN:
152100
Hom.:
1
Cov.:
32
AF XY:
0.000229
AC XY:
17
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.000361
Gnomad4 AMR
AF:
0.000393
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000624
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000115
Hom.:
0
Bravo
AF:
0.000227
ESP6500AA
AF:
0.000681
AC:
3
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000264
AC:
32
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Benign:1
Mar 16, 2022
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This 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
0.074
BayesDel_addAF
Benign
-0.68
T
BayesDel_noAF
Benign
-0.82
CADD
Benign
7.0
DANN
Benign
0.79
DEOGEN2
Benign
0.024
T;.;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.000040
N
LIST_S2
Benign
0.050
T;.;T;T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.011
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;.;.;.
PrimateAI
Benign
0.24
T
PROVEAN
Benign
0.55
N;N;.;.
REVEL
Benign
0.021
Sift
Benign
0.29
T;T;.;.
Sift4G
Benign
0.091
T;T;T;T
Polyphen
0.0
B;.;B;.
Vest4
0.031
MVP
0.32
MPC
0.28
ClinPred
0.0026
T
GERP RS
-0.37
Varity_R
0.016
gMVP
0.21

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: rs370163168; hg19: chr19-37210234; COSMIC: COSV62444025; API