chr19-57686895-G-C

Variant summary

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

The NM_138347.5(ZNF551):ā€‹c.620G>Cā€‹(p.Ser207Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000222 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00022 ( 0 hom., cov: 33)
Exomes š‘“: 0.00022 ( 0 hom. )

Consequence

ZNF551
NM_138347.5 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.41
Variant links:
Genes affected
ZNF551 (HGNC:25108): (zinc finger protein 551) 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=0.014395207).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF551NM_138347.5 linkuse as main transcriptc.620G>C p.Ser207Thr missense_variant 3/3 ENST00000282296.10 NP_612356.2
ZNF551NM_001270938.2 linkuse as main transcriptc.536G>C p.Ser179Thr missense_variant 3/3 NP_001257867.1
ZNF551NR_073102.2 linkuse as main transcriptn.683G>C non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF551ENST00000282296.10 linkuse as main transcriptc.620G>C p.Ser207Thr missense_variant 3/31 NM_138347.5 ENSP00000282296 P1Q7Z340-1
ZNF551ENST00000601064.1 linkuse as main transcriptc.536G>C p.Ser179Thr missense_variant 3/31 ENSP00000472674
ZNF551ENST00000596085.1 linkuse as main transcriptc.157+1510G>C intron_variant 2 ENSP00000472230

Frequencies

GnomAD3 genomes
AF:
0.000210
AC:
32
AN:
152222
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000392
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000220
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000255
AC:
64
AN:
251058
Hom.:
0
AF XY:
0.000191
AC XY:
26
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.000247
Gnomad AMR exome
AF:
0.000434
Gnomad ASJ exome
AF:
0.00219
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000176
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000222
AC:
325
AN:
1461872
Hom.:
0
Cov.:
31
AF XY:
0.000217
AC XY:
158
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.000329
Gnomad4 AMR exome
AF:
0.000492
Gnomad4 ASJ exome
AF:
0.00184
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000192
Gnomad4 OTH exome
AF:
0.000364
GnomAD4 genome
AF:
0.000223
AC:
34
AN:
152340
Hom.:
0
Cov.:
33
AF XY:
0.000107
AC XY:
8
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.000216
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000220
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000336
Hom.:
0
Bravo
AF:
0.000283
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000189
AC:
23
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000237

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 GeneticsSep 16, 2021The c.572G>C (p.S191T) alteration is located in exon 3 (coding exon 3) of the ZNF551 gene. This alteration results from a G to C substitution at nucleotide position 572, causing the serine (S) at amino acid position 191 to be replaced by a threonine (T). 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
0.067
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
5.4
DANN
Benign
0.69
DEOGEN2
Benign
0.016
T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.00018
N
LIST_S2
Benign
0.029
T;T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.014
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
.;L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.20
T
REVEL
Benign
0.012
Sift4G
Benign
0.33
T;T
Polyphen
0.017
.;B
Vest4
0.085
MVP
0.16
MPC
0.16
ClinPred
0.011
T
GERP RS
0.47
Varity_R
0.056
gMVP
0.0061

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: rs140247514; hg19: chr19-58198263; API