3-44447500-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_181489.6(ZNF445):ā€‹c.2171T>Cā€‹(p.Phe724Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,890 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 (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

ZNF445
NM_181489.6 missense

Scores

1
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.877
Variant links:
Genes affected
ZNF445 (HGNC:21018): (zinc finger protein 445) Enables double-stranded methylated DNA binding activity. Involved in maintenance of DNA methylation and regulation of genetic imprinting. Located 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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33341658).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF445NM_181489.6 linkc.2171T>C p.Phe724Ser missense_variant 8/8 ENST00000396077.8 NP_852466.1 P59923
ZNF445NM_001369454.1 linkc.2135T>C p.Phe712Ser missense_variant 7/7 NP_001356383.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF445ENST00000396077.8 linkc.2171T>C p.Phe724Ser missense_variant 8/81 NM_181489.6 ENSP00000379387.2 P59923
ZNF445ENST00000425708.6 linkc.2171T>C p.Phe724Ser missense_variant 6/61 ENSP00000413073.2 P59923

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251130
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135710
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsMay 26, 2023The c.2171T>C (p.F724S) alteration is located in exon 8 (coding exon 6) of the ZNF445 gene. This alteration results from a T to C substitution at nucleotide position 2171, causing the phenylalanine (F) at amino acid position 724 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
Pathogenic
0.88
BayesDel_addAF
Benign
-0.0066
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.32
T;T
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.82
FATHMM_MKL
Benign
0.088
N
M_CAP
Uncertain
0.093
D
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-3.4
D;D
REVEL
Benign
0.29
Sift
Uncertain
0.011
D;D
Sift4G
Uncertain
0.0080
D;D
Polyphen
0.40
B;B
Vest4
0.35
MutPred
0.70
Loss of stability (P = 5e-04);Loss of stability (P = 5e-04);
MVP
0.71
MPC
0.46
ClinPred
0.56
D
GERP RS
-0.45
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.25
gMVP
0.43

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: rs1364193195; hg19: chr3-44488992; API