16-89722600-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001113525.2(ZNF276):​c.275G>A​(p.Arg92His) variant causes a missense change. The variant allele was found at a frequency of 0.0000329 in 1,612,044 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 0.000026 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

ZNF276
NM_001113525.2 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.95

Publications

0 publications found
Variant links:
Genes affected
ZNF276 (HGNC:23330): (zinc finger protein 276) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in kinetochore. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36344764).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF276NM_001113525.2 linkc.275G>A p.Arg92His missense_variant Exon 2 of 11 ENST00000443381.7 NP_001106997.1 Q8N554-1I6L9I3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF276ENST00000443381.7 linkc.275G>A p.Arg92His missense_variant Exon 2 of 11 1 NM_001113525.2 ENSP00000415836.2 Q8N554-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152258
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000321
AC:
8
AN:
249410
AF XY:
0.0000295
show subpopulations
Gnomad AFR exome
AF:
0.0000623
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000622
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000336
AC:
49
AN:
1459786
Hom.:
0
Cov.:
31
AF XY:
0.0000344
AC XY:
25
AN XY:
726236
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44718
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51390
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000396
AC:
44
AN:
1111972
Other (OTH)
AF:
0.0000663
AC:
4
AN:
60372
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.490
Heterozygous variant carriers
0
4
8
11
15
19
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152258
Hom.:
0
Cov.:
34
AF XY:
0.0000269
AC XY:
2
AN XY:
74392
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41476
American (AMR)
AF:
0.00
AC:
0
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5194
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000588
AC:
4
AN:
68046
Other (OTH)
AF:
0.00
AC:
0
AN:
2094
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000847
Hom.:
0
Bravo
AF:
0.0000453
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 08, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.275G>A (p.R92H) alteration is located in exon 2 (coding exon 2) of the ZNF276 gene. This alteration results from a G to A substitution at nucleotide position 275, causing the arginine (R) at amino acid position 92 to be replaced by a histidine (H). 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
Benign
0.29
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.32
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.025
.;T;T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.36
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.5
.;.;M
PhyloP100
4.9
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.6
N;N;N
REVEL
Benign
0.25
Sift
Uncertain
0.0020
D;D;D
Sift4G
Benign
0.091
T;T;T
Polyphen
1.0
D;.;D
Vest4
0.52
MVP
0.16
MPC
0.45
ClinPred
0.39
T
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.34
gMVP
0.39
Mutation Taster
=89/11
polymorphism

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

Other links and lift over

dbSNP: rs374183133; hg19: chr16-89789008; COSMIC: COSV105863417; API