chr19-52384127-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145434.2(ZNF880):​c.547C>T​(p.Pro183Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000687 in 1,602,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

ZNF880
NM_001145434.2 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.591
Variant links:
Genes affected
ZNF880 (HGNC:37249): (zinc finger protein 880) 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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08739504).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF880NM_001145434.2 linkc.547C>T p.Pro183Ser missense_variant Exon 4 of 4 ENST00000422689.3 NP_001138906.1 Q6PDB4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF880ENST00000422689.3 linkc.547C>T p.Pro183Ser missense_variant Exon 4 of 4 2 NM_001145434.2 ENSP00000406318.2 Q6PDB4-1
ZNF880ENST00000424032.6 linkc.*289C>T downstream_gene_variant 4 ENSP00000414470.2 F5H026

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152194
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000868
AC:
2
AN:
230524
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
124994
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000119
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000690
AC:
10
AN:
1450006
Hom.:
0
Cov.:
41
AF XY:
0.00000416
AC XY:
3
AN XY:
720418
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000763
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000543
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152312
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 18, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.547C>T (p.P183S) alteration is located in exon 4 (coding exon 4) of the ZNF880 gene. This alteration results from a C to T substitution at nucleotide position 547, causing the proline (P) at amino acid position 183 to be replaced by a serine (S). 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
0.084
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
6.2
DANN
Benign
0.58
DEOGEN2
Benign
0.021
T
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.016
N
LIST_S2
Benign
0.15
T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.087
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
M
PrimateAI
Benign
0.22
T
PROVEAN
Pathogenic
-5.6
D
REVEL
Benign
0.051
Sift
Benign
0.24
T
Sift4G
Benign
0.17
T
Polyphen
0.95
P
Vest4
0.16
MutPred
0.38
Loss of catalytic residue at P183 (P = 8e-04);
MVP
0.13
MPC
0.049
ClinPred
0.41
T
GERP RS
1.7
Varity_R
0.049
gMVP
0.017

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: rs543687016; hg19: chr19-52887380; COSMIC: COSV69907027; COSMIC: COSV69907027; API