1-248855429-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_017865.4(ZNF692):​c.989G>A​(p.Cys330Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZNF692
NM_017865.4 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.26
Variant links:
Genes affected
ZNF692 (HGNC:26049): (zinc finger protein 692) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II and regulation of gluconeogenesis. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.978

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF692NM_017865.4 linkc.989G>A p.Cys330Tyr missense_variant Exon 9 of 12 ENST00000306601.9 NP_060335.2 Q9BU19-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF692ENST00000306601.9 linkc.989G>A p.Cys330Tyr missense_variant Exon 9 of 12 1 NM_017865.4 ENSP00000305483.5 Q9BU19-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 19, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1004G>A (p.C335Y) alteration is located in exon 9 (coding exon 9) of the ZNF692 gene. This alteration results from a G to A substitution at nucleotide position 1004, causing the cysteine (C) at amino acid position 335 to be replaced by a tyrosine (Y). 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
Pathogenic
1.0
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
T;.;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.025
D
MetaRNN
Pathogenic
0.98
D;D;D
MetaSVM
Benign
-0.90
T
MutationAssessor
Uncertain
2.8
M;.;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-9.6
D;D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0020
D;D;D
Sift4G
Benign
0.13
T;T;T
Polyphen
1.0
D;D;.
Vest4
0.88
MutPred
0.93
Gain of MoRF binding (P = 0.0781);.;.;
MVP
0.31
MPC
0.98
ClinPred
1.0
D
GERP RS
4.1
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.85
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs865909791; hg19: chr1-249149628; API