1-42851490-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001242739.2(ZNF691):āc.625A>Cā(p.Ser209Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,614,092 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 (ā ).
Frequency
Genomes: š 0.000072 ( 0 hom., cov: 32)
Exomes š: 0.000042 ( 0 hom. )
Consequence
ZNF691
NM_001242739.2 missense
NM_001242739.2 missense
Scores
1
3
15
Clinical Significance
Conservation
PhyloP100: -0.188
Genes affected
ZNF691 (HGNC:28028): (zinc finger protein 691) Predicted to enable DNA-binding transcription factor activity 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 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=0.10640311).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF691 | NM_001242739.2 | c.625A>C | p.Ser209Arg | missense_variant | 4/4 | ENST00000651192.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF691 | ENST00000651192.1 | c.625A>C | p.Ser209Arg | missense_variant | 4/4 | NM_001242739.2 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152228Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000680 AC: 17AN: 249966Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135208
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GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 727234
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74376
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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 | Jun 06, 2023 | The c.625A>C (p.S209R) alteration is located in exon 4 (coding exon 2) of the ZNF691 gene. This alteration results from a A to C substitution at nucleotide position 625, causing the serine (S) at amino acid position 209 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;.;.;T;.;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.;.;.;.
MutationTaster
Benign
N;N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
.;D;D;D;D;D;.
REVEL
Benign
Sift
Benign
.;T;T;T;T;T;.
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
B;.;.;.;.;.;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0144);.;.;.;.;Gain of MoRF binding (P = 0.0144);.;
MVP
ClinPred
T
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