16-3223922-G-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_198088.3(ZNF200):c.1158C>A(p.His386Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,734 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 1 hom. )
Consequence
ZNF200
NM_198088.3 missense
NM_198088.3 missense
Scores
4
6
9
Clinical Significance
Conservation
PhyloP100: 0.849
Genes affected
ZNF200 (HGNC:12993): (zinc finger protein 200) Predicted to enable metal ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
OR1F1 (HGNC:8194): (olfactory receptor family 1 subfamily F member 1) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38608938).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZNF200 | NM_198088.3 | c.1158C>A | p.His386Gln | missense_variant | 5/5 | ENST00000414144.7 | NP_932354.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNF200 | ENST00000414144.7 | c.1158C>A | p.His386Gln | missense_variant | 5/5 | 1 | NM_198088.3 | ENSP00000405786 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
1
AN:
152172
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 250994Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135660
GnomAD3 exomes
AF:
AC:
10
AN:
250994
Hom.:
AF XY:
AC XY:
5
AN XY:
135660
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461562Hom.: 1 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727092
GnomAD4 exome
AF:
AC:
39
AN:
1461562
Hom.:
Cov.:
31
AF XY:
AC XY:
14
AN XY:
727092
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74344
GnomAD4 genome
AF:
AC:
1
AN:
152172
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74344
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
5
Asia WGS
AF:
AC:
1
AN:
3478
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 submitter | clinical testing | Ambry Genetics | May 25, 2022 | The c.1158C>A (p.H386Q) alteration is located in exon 5 (coding exon 4) of the ZNF200 gene. This alteration results from a C to A substitution at nucleotide position 1158, causing the histidine (H) at amino acid position 386 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.;.;T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
.;H;.;H;.;.
MutationTaster
Benign
N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D;D;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;.;.
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
D;P;.;P;.;.
Vest4
MutPred
0.29
.;Loss of helix (P = 0.1299);.;Loss of helix (P = 0.1299);.;.;
MVP
MPC
0.021
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at