chr20-45949561-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_022095.4(ZNF335):āc.3677A>Gā(p.Tyr1226Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,611,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.000024 ( 0 hom. )
Consequence
ZNF335
NM_022095.4 missense
NM_022095.4 missense
Scores
6
7
6
Clinical Significance
Conservation
PhyloP100: 7.37
Genes affected
ZNF335 (HGNC:15807): (zinc finger protein 335) The protein encoded by this gene enhances transcriptional activation by ligand-bound nuclear hormone receptors. However, it does this not by direct interaction with the receptor, but by direct interaction with the nuclear hormone receptor transcriptional coactivator NRC. The encoded protein may function by altering local chromatin structure. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.852
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF335 | NM_022095.4 | c.3677A>G | p.Tyr1226Cys | missense_variant | 25/28 | ENST00000322927.3 | |
ZNF335 | XM_047440363.1 | c.3677A>G | p.Tyr1226Cys | missense_variant | 24/27 | ||
ZNF335 | XM_005260504.5 | c.3674A>G | p.Tyr1225Cys | missense_variant | 24/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF335 | ENST00000322927.3 | c.3677A>G | p.Tyr1226Cys | missense_variant | 25/28 | 1 | NM_022095.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152008Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000240 AC: 35AN: 1459336Hom.: 0 Cov.: 32 AF XY: 0.0000207 AC XY: 15AN XY: 725886
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152008Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74250
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Nov 03, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Loss of phosphorylation at Y1226 (P = 0.0714);
MVP
MPC
ClinPred
D
GERP RS
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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