1-248850752-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017865.4(ZNF692):​c.1183G>A​(p.Ala395Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ZNF692
NM_017865.4 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.47
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF692NM_017865.4 linkc.1183G>A p.Ala395Thr missense_variant Exon 11 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.1183G>A p.Ala395Thr missense_variant Exon 11 of 12 1 NM_017865.4 ENSP00000305483.5 Q9BU19-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152104
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000438
AC:
11
AN:
251422
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000109
AC:
16
AN:
1461872
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152104
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1198G>A (p.A400T) alteration is located in exon 11 (coding exon 11) of the ZNF692 gene. This alteration results from a G to A substitution at nucleotide position 1198, causing the alanine (A) at amino acid position 400 to be replaced by a threonine (T). 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
Uncertain
0.51
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.38
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.22
T;.;.
Eigen
Benign
0.16
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.047
D
MetaRNN
Uncertain
0.46
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.85
L;.;.
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-3.0
D;D;D
REVEL
Benign
0.21
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.0040
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.58
MutPred
0.65
Loss of catalytic residue at A395 (P = 0.0929);.;.;
MVP
0.067
MPC
0.72
ClinPred
0.58
D
GERP RS
4.4
Varity_R
0.26
gMVP
0.19

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: rs751034714; hg19: chr1-249144951; API