chr7-64348840-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001170905.3(ZNF736):c.977C>T(p.Ser326Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,596,574 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 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00034 ( 0 hom. )
Consequence
ZNF736
NM_001170905.3 missense
NM_001170905.3 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: -0.343
Genes affected
ZNF736 (HGNC:32467): (zinc finger protein 736) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. 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=0.12025455).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF736 | NM_001170905.3 | c.977C>T | p.Ser326Leu | missense_variant | 4/4 | ENST00000423484.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF736 | ENST00000423484.3 | c.977C>T | p.Ser326Leu | missense_variant | 4/4 | 2 | NM_001170905.3 | P1 | |
ZNF736 | ENST00000355095.8 | c.977C>T | p.Ser326Leu | missense_variant | 5/5 | 5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152110Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000104 AC: 23AN: 221540Hom.: 0 AF XY: 0.000117 AC XY: 14AN XY: 119892
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GnomAD4 exome AF: 0.000342 AC: 494AN: 1444346Hom.: 0 Cov.: 32 AF XY: 0.000343 AC XY: 246AN XY: 717210
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74414
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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 | Jul 13, 2021 | The c.977C>T (p.S326L) alteration is located in exon 5 (coding exon 4) of the ZNF736 gene. This alteration results from a C to T substitution at nucleotide position 977, causing the serine (S) at amino acid position 326 to be replaced by a leucine (L). 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
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Benign
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of catalytic residue at S326 (P = 0.0029);Loss of catalytic residue at S326 (P = 0.0029);
MVP
MPC
0.26
ClinPred
T
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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