chr19-9653739-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001130031.2(ZNF562):​c.491G>A​(p.Ser164Asn) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ZNF562
NM_001130031.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.04
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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.057724386).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF562NM_001130031.2 linkc.491G>A p.Ser164Asn 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.491G>A p.Ser164Asn missense_variant Exon 6 of 6 3 NM_001130031.2 ENSP00000410734.1 Q6V9R5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251278
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135802
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000410
AC:
6
AN:
1461784
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.491G>A (p.S164N) alteration is located in exon 6 (coding exon 5) of the ZNF562 gene. This alteration results from a G to A substitution at nucleotide position 491, causing the serine (S) at amino acid position 164 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.075
DANN
Benign
0.70
DEOGEN2
Benign
0.0081
.;T;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.0034
N
LIST_S2
Benign
0.78
T;T;T
M_CAP
Benign
0.00040
T
MetaRNN
Benign
0.058
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.39
.;N;.
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-0.93
N;N;.
REVEL
Benign
0.016
Sift
Benign
0.17
T;T;.
Sift4G
Benign
0.17
T;T;T
Polyphen
0.40
B;B;.
Vest4
0.038
MutPred
0.23
.;Loss of disorder (P = 0.0883);.;
MVP
0.085
ClinPred
0.045
T
GERP RS
-2.9
Varity_R
0.037
gMVP
0.024

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: rs760986308; hg19: chr19-9764415; API