8-143295769-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_030895.3(ZNF696):​c.94C>T​(p.Pro32Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,603,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

ZNF696
NM_030895.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.77
Variant links:
Genes affected
ZNF696 (HGNC:25872): (zinc finger protein 696) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05041662).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF696NM_030895.3 linkc.94C>T p.Pro32Ser missense_variant Exon 3 of 3 ENST00000330143.8 NP_112157.2 Q9H7X3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF696ENST00000330143.8 linkc.94C>T p.Pro32Ser missense_variant Exon 3 of 3 1 NM_030895.3 ENSP00000328515.3 Q9H7X3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152258
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000276
AC:
4
AN:
1451250
Hom.:
0
Cov.:
29
AF XY:
0.00000139
AC XY:
1
AN XY:
721292
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:
0.00000271
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152258
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000846
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 30, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.94C>T (p.P32S) alteration is located in exon 3 (coding exon 2) of the ZNF696 gene. This alteration results from a C to T substitution at nucleotide position 94, causing the proline (P) at amino acid position 32 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.013
DANN
Benign
0.96
DEOGEN2
Benign
0.016
.;.;T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0056
N
LIST_S2
Benign
0.45
T;T;T;T
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.050
T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.34
.;.;N;.
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-6.3
D;N;N;D
REVEL
Benign
0.037
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Benign
0.15
T;T;T;T
Polyphen
0.0050
.;.;B;.
Vest4
0.036
MutPred
0.23
.;Gain of MoRF binding (P = 0.0391);Gain of MoRF binding (P = 0.0391);Gain of MoRF binding (P = 0.0391);
MVP
0.048
MPC
0.74
ClinPred
0.14
T
GERP RS
-3.8
Varity_R
0.043
gMVP
0.14

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777128472; hg19: chr8-144377939; API