19-53407731-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040185.3(ZNF765):​c.176C>G​(p.Ser59Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,415,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S59L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.1e-7 ( 0 hom. )

Consequence

ZNF765
NM_001040185.3 missense

Scores

3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.11
Variant links:
Genes affected
ZNF765 (HGNC:25092): (zinc finger protein 765) 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 by RNA polymerase II. Predicted to be active 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=0.1911822).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF765NM_001040185.3 linkc.176C>G p.Ser59Trp missense_variant Exon 4 of 4 ENST00000396408.8 NP_001035275.1 Q7L2R6-1
ZNF765NM_001350495.2 linkc.17C>G p.Ser6Trp missense_variant Exon 3 of 3 NP_001337424.1
ZNF765-ZNF761NM_001350496.2 linkc.-1345+5540C>G intron_variant Intron 3 of 12 NP_001337425.1
ZNF765NR_146721.2 linkn.260+5540C>G intron_variant Intron 3 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF765ENST00000396408.8 linkc.176C>G p.Ser59Trp missense_variant Exon 4 of 4 1 NM_001040185.3 ENSP00000379689.3 Q7L2R6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.06e-7
AC:
1
AN:
1415626
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
700394
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.16e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
0.61
DANN
Benign
0.59
DEOGEN2
Benign
0.055
T;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0034
N
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.6
M;.
PROVEAN
Uncertain
-3.9
D;D
REVEL
Benign
0.049
Sift
Benign
0.080
T;D
Sift4G
Benign
0.18
T;T
Polyphen
0.99
D;.
Vest4
0.23
MutPred
0.43
Loss of disorder (P = 1e-04);.;
MVP
0.16
MPC
0.32
ClinPred
0.36
T
GERP RS
-2.0
Varity_R
0.061
gMVP
0.019

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-53910984; API