19-53576886-A-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001079906.2(ZNF331):c.326A>T(p.Lys109Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00662 in 1,614,130 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0055 ( 4 hom., cov: 33)
Exomes 𝑓: 0.0067 ( 47 hom. )
Consequence
ZNF331
NM_001079906.2 missense
NM_001079906.2 missense
Scores
1
12
Clinical Significance
Conservation
PhyloP100: 0.989
Genes affected
ZNF331 (HGNC:15489): (zinc finger protein 331) This gene encodes a zinc finger protein containing a KRAB (Kruppel-associated box) domain found in transcriptional repressors. This gene may be methylated and silenced in cancer cells. This gene is located within a differentially methylated region (DMR) and shows allele-specific expression in placenta. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding the same protein. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.007546127).
BP6
?
Variant 19-53576886-A-T is Benign according to our data. Variant chr19-53576886-A-T is described in ClinVar as [Benign]. Clinvar id is 771042.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High Homozygotes in GnomAd at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF331 | NM_001079906.2 | c.326A>T | p.Lys109Ile | missense_variant | 6/6 | ENST00000449416.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF331 | ENST00000449416.6 | c.326A>T | p.Lys109Ile | missense_variant | 6/6 | 5 | NM_001079906.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00549 AC: 836AN: 152168Hom.: 4 Cov.: 33
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GnomAD3 exomes AF: 0.00665 AC: 1672AN: 251390Hom.: 10 AF XY: 0.00662 AC XY: 899AN XY: 135868
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GnomAD4 exome AF: 0.00673 AC: 9842AN: 1461844Hom.: 47 Cov.: 30 AF XY: 0.00670 AC XY: 4869AN XY: 727222
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GnomAD4 genome ? AF: 0.00549 AC: 836AN: 152286Hom.: 4 Cov.: 33 AF XY: 0.00521 AC XY: 388AN XY: 74454
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jun 01, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;L;L;L;L;L;L;.;.;L;L;L
MutationTaster
Benign
D;N;N;N;N;N;N;N
PrimateAI
Benign
T
Polyphen
B;B;B;B;B;B;B;B;B;B;.;.;B;B;B
Vest4
0.27, 0.34, 0.31, 0.33, 0.28, 0.30, 0.28
MVP
0.47
MPC
1.4
ClinPred
T
GERP RS
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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