19-9653745-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001130031.2(ZNF562):​c.485G>T​(p.Ser162Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

ZNF562
NM_001130031.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.161
Variant links:
Genes affected
ZNF562 (HGNC:25950): (zinc finger protein 562) Predicted to enable DNA-binding transcription factor 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
ZNF561-AS1 (HGNC:27613): (ZNF561 antisense RNA 1 (head to head))

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0423761).
BP6
Variant 19-9653745-C-A is Benign according to our data. Variant chr19-9653745-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2511152.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF562NM_001130031.2 linkc.485G>T p.Ser162Ile missense_variant Exon 6 of 6 ENST00000453372.7 NP_001123503.1 Q6V9R5-1A0A024R7A3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF562ENST00000453372.7 linkc.485G>T p.Ser162Ile missense_variant Exon 6 of 6 3 NM_001130031.2 ENSP00000410734.1 Q6V9R5-1

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152182
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000314
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000123
AC:
31
AN:
251314
Hom.:
0
AF XY:
0.0000810
AC XY:
11
AN XY:
135820
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000229
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000275
AC:
402
AN:
1461790
Hom.:
0
Cov.:
31
AF XY:
0.000250
AC XY:
182
AN XY:
727188
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000352
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152300
Hom.:
0
Cov.:
33
AF XY:
0.000134
AC XY:
10
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.000337
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00409
Hom.:
59
Bravo
AF:
0.000159
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000123
AC:
15
EpiCase
AF:
0.000654
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not specified Benign:1
Jun 13, 2023
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
0.10
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
2.6
DANN
Benign
0.18
DEOGEN2
Benign
0.0062
.;T;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.00038
N
LIST_S2
Benign
0.44
T;T;T
M_CAP
Benign
0.00089
T
MetaRNN
Benign
0.042
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.14
.;N;.
PrimateAI
Benign
0.23
T
PROVEAN
Benign
1.1
N;N;.
REVEL
Benign
0.023
Sift
Benign
0.42
T;T;.
Sift4G
Benign
0.14
T;T;T
Polyphen
0.0
B;B;.
Vest4
0.042
MVP
0.12
ClinPred
0.0029
T
GERP RS
1.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.033
gMVP
0.069

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: rs200076265; hg19: chr19-9764421; API