7-112286899-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_021994.3(ZNF277):c.118C>T(p.Leu40Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,559,992 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 0.000054 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
ZNF277
NM_021994.3 missense
NM_021994.3 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 3.08
Genes affected
ZNF277 (HGNC:13070): (zinc finger protein 277) Predicted to enable RNA polymerase II cis-regulatory region sequence-specific DNA binding activity and metal ion binding activity. Predicted to act upstream of or within cellular response to hydrogen peroxide and regulation of cellular senescence. Predicted to be located 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=0.2631972).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF277 | NM_021994.3 | c.118C>T | p.Leu40Phe | missense_variant | 2/12 | ENST00000361822.8 | |
ZNF277 | XM_011515768.4 | c.-117C>T | 5_prime_UTR_variant | 2/12 | |||
ZNF277 | XM_017011720.3 | c.-148C>T | 5_prime_UTR_variant | 2/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF277 | ENST00000361822.8 | c.118C>T | p.Leu40Phe | missense_variant | 2/12 | 1 | NM_021994.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000539 AC: 7AN: 129966Hom.: 0 Cov.: 29
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250964Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135650
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GnomAD4 exome AF: 0.0000196 AC: 28AN: 1430026Hom.: 0 Cov.: 34 AF XY: 0.0000169 AC XY: 12AN XY: 711826
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GnomAD4 genome ? AF: 0.0000539 AC: 7AN: 129966Hom.: 0 Cov.: 29 AF XY: 0.0000326 AC XY: 2AN XY: 61268
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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, 2022 | The c.118C>T (p.L40F) alteration is located in exon 2 (coding exon 2) of the ZNF277 gene. This alteration results from a C to T substitution at nucleotide position 118, causing the leucine (L) at amino acid position 40 to be replaced by a phenylalanine (F). 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
Pathogenic
DEOGEN2
Benign
T;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;N;D
REVEL
Benign
Sift
Uncertain
D;D;T;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;.;.;D
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