chr19-37412755-C-T

Variant summary

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

The NM_152484.3(ZNF569):​c.1903G>A​(p.Asp635Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

ZNF569
NM_152484.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.685
Variant links:
Genes affected
ZNF569 (HGNC:24737): (zinc finger protein 569) 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 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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0547899).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF569NM_152484.3 linkuse as main transcriptc.1903G>A p.Asp635Asn missense_variant 6/6 ENST00000316950.11 NP_689697.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF569ENST00000316950.11 linkuse as main transcriptc.1903G>A p.Asp635Asn missense_variant 6/61 NM_152484.3 ENSP00000325018 P2Q5MCW4-1
ZNF569ENST00000392149.6 linkuse as main transcriptc.1903G>A p.Asp635Asn missense_variant 5/51 ENSP00000375992 P2Q5MCW4-1
ZNF569ENST00000392150.2 linkuse as main transcriptc.1426G>A p.Asp476Asn missense_variant 2/21 ENSP00000375993 Q5MCW4-2
ZNF569ENST00000448051.7 linkuse as main transcriptc.1975G>A p.Asp659Asn missense_variant 9/92 ENSP00000466221 A2

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152112
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251200
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135764
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000527
AC:
77
AN:
1461744
Hom.:
0
Cov.:
32
AF XY:
0.0000481
AC XY:
35
AN XY:
727166
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000612
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152230
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000315
Hom.:
0
Bravo
AF:
0.0000567
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000218
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 30, 2024The c.1903G>A (p.D635N) alteration is located in exon 6 (coding exon 4) of the ZNF569 gene. This alteration results from a G to A substitution at nucleotide position 1903, causing the aspartic acid (D) at amino acid position 635 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
0.10
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.77
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.031
T;T;.
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.029
N
LIST_S2
Benign
0.76
.;T;T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.055
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.13
N;N;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-0.62
.;N;N
REVEL
Benign
0.092
Sift
Benign
0.12
.;T;T
Sift4G
Uncertain
0.025
D;D;D
Polyphen
0.49
P;P;.
Vest4
0.21
MVP
0.38
MPC
0.58
ClinPred
0.11
T
GERP RS
4.1
Varity_R
0.084
gMVP
0.036

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: rs199656641; hg19: chr19-37903657; COSMIC: COSV57594303; COSMIC: COSV57594303; API