19-44131636-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_013362.4(ZNF225):c.1022A>G(p.Glu341Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
ZNF225
NM_013362.4 missense
NM_013362.4 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 4.39
Genes affected
ZNF225 (HGNC:13018): (zinc finger protein 225) Predicted to enable DNA-binding transcription activator 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]
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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=0.18365529).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF225 | NM_013362.4 | c.1022A>G | p.Glu341Gly | missense_variant | 5/5 | ENST00000262894.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF225 | ENST00000262894.11 | c.1022A>G | p.Glu341Gly | missense_variant | 5/5 | 1 | NM_013362.4 | P1 | |
ZNF225 | ENST00000590612.1 | c.1022A>G | p.Glu341Gly | missense_variant | 4/4 | 1 | P1 | ||
ZNF225 | ENST00000592780.5 | c.*803A>G | 3_prime_UTR_variant | 6/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152178Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250578Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135774
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461794Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727200
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74326
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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 submitter | clinical testing | Ambry Genetics | Oct 05, 2023 | The c.1022A>G (p.E341G) alteration is located in exon 5 (coding exon 4) of the ZNF225 gene. This alteration results from a A to G substitution at nucleotide position 1022, causing the glutamic acid (E) at amino acid position 341 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;N;N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at