1-42851490-A-C

Variant summary

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

The NM_001242739.2(ZNF691):ā€‹c.625A>Cā€‹(p.Ser209Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,614,092 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000072 ( 0 hom., cov: 32)
Exomes š‘“: 0.000042 ( 0 hom. )

Consequence

ZNF691
NM_001242739.2 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.188
Variant links:
Genes affected
ZNF691 (HGNC:28028): (zinc finger protein 691) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10640311).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF691NM_001242739.2 linkuse as main transcriptc.625A>C p.Ser209Arg missense_variant 4/4 ENST00000651192.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF691ENST00000651192.1 linkuse as main transcriptc.625A>C p.Ser209Arg missense_variant 4/4 NM_001242739.2 Q5VV52-2

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152228
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
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:
0.0000588
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.0000680
AC:
17
AN:
249966
Hom.:
0
AF XY:
0.0000444
AC XY:
6
AN XY:
135208
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000889
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.0000417
AC:
61
AN:
1461864
Hom.:
0
Cov.:
31
AF XY:
0.0000303
AC XY:
22
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000179
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:
0.0000369
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152228
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.000955
Alfa
AF:
0.0000565
Hom.:
0
Bravo
AF:
0.000181
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

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 submitterclinical testingAmbry GeneticsJun 06, 2023The c.625A>C (p.S209R) alteration is located in exon 4 (coding exon 2) of the ZNF691 gene. This alteration results from a A to C substitution at nucleotide position 625, causing the serine (S) at amino acid position 209 to be replaced by an arginine (R). 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
0.93
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;.;.;.;T;T;T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.35
T;.;.;T;.;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.11
T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.055
N;.;.;.;.;.;.
MutationTaster
Benign
0.92
N;N;N;N;N;N;N
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-3.7
.;D;D;D;D;D;.
REVEL
Benign
0.056
Sift
Benign
0.17
.;T;T;T;T;T;.
Sift4G
Benign
0.065
T;T;T;T;T;T;T
Polyphen
0.34
B;.;.;.;.;.;.
Vest4
0.15
MutPred
0.54
Gain of MoRF binding (P = 0.0144);.;.;.;.;Gain of MoRF binding (P = 0.0144);.;
MVP
0.014
ClinPred
0.099
T
GERP RS
1.6
Varity_R
0.26
gMVP
0.095

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: rs367817475; hg19: chr1-43317161; API