16-3224170-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_198088.3(ZNF200):​c.910G>A​(p.Gly304Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,614,032 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZNF200
NM_198088.3 missense

Scores

5
3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.05
Variant links:
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=0.31551826).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF200NM_198088.3 linkc.910G>A p.Gly304Arg missense_variant Exon 5 of 5 ENST00000414144.7 NP_932354.1 P98182-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF200ENST00000414144.7 linkc.910G>A p.Gly304Arg missense_variant Exon 5 of 5 1 NM_198088.3 ENSP00000405786.2 P98182-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152158
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251042
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135640
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152158
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74328
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 09, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.910G>A (p.G304R) alteration is located in exon 5 (coding exon 4) of the ZNF200 gene. This alteration results from a G to A substitution at nucleotide position 910, causing the glycine (G) at amino acid position 304 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
0.97
BayesDel_addAF
Benign
-0.090
T
BayesDel_noAF
Benign
-0.37
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
.;T;.;T;.;.
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Benign
0.055
N
LIST_S2
Benign
0.69
T;.;.;T;.;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.32
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.97
.;L;.;L;.;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-8.0
D;.;D;D;.;.
REVEL
Benign
0.22
Sift
Pathogenic
0.0
D;.;D;D;.;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D
Polyphen
1.0
D;D;.;D;.;.
Vest4
0.45
MutPred
0.32
.;Gain of solvent accessibility (P = 0.0037);.;Gain of solvent accessibility (P = 0.0037);.;.;
MVP
0.27
MPC
0.048
ClinPred
1.0
D
GERP RS
4.4
Varity_R
0.78
gMVP
0.11

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: rs889659891; hg19: chr16-3274170; API