20-45948962-G-A
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_022095.4(ZNF335):c.4020C>T(p.Ala1340=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,756 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
ZNF335
NM_022095.4 synonymous
NM_022095.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.63
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 Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
?
Variant 20-45948962-G-A is Benign according to our data. Variant chr20-45948962-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1905624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.63 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF335 | NM_022095.4 | c.4020C>T | p.Ala1340= | synonymous_variant | 28/28 | ENST00000322927.3 | |
ZNF335 | XM_047440363.1 | c.4020C>T | p.Ala1340= | synonymous_variant | 27/27 | ||
ZNF335 | XM_005260504.5 | c.4017C>T | p.Ala1339= | synonymous_variant | 27/27 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF335 | ENST00000322927.3 | c.4020C>T | p.Ala1340= | synonymous_variant | 28/28 | 1 | NM_022095.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251186Hom.: 1 AF XY: 0.0000221 AC XY: 3AN XY: 135866
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GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461556Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14AN XY: 727094
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
ZNF335-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 02, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 02, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at