16-89722641-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001113525.2(ZNF276):​c.316C>G​(p.Pro106Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Consequence

ZNF276
NM_001113525.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.831
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.058242172).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF276NM_001113525.2 linkc.316C>G p.Pro106Ala 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.316C>G p.Pro106Ala missense_variant Exon 2 of 11 1 NM_001113525.2 ENSP00000415836.2 Q8N554-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
34

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 03, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.316C>G (p.P106A) alteration is located in exon 2 (coding exon 2) of the ZNF276 gene. This alteration results from a C to G substitution at nucleotide position 316, causing the proline (P) at amino acid position 106 to be replaced by an alanine (A). 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
0.10
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
0.86
DANN
Benign
0.41
DEOGEN2
Benign
0.0052
.;T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.47
T;T;T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.058
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.9
.;.;L
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.21
N;N;N
REVEL
Benign
0.015
Sift
Benign
0.45
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.17
B;.;B
Vest4
0.31
MutPred
0.36
.;.;Loss of glycosylation at P106 (P = 0.0453);
MVP
0.014
MPC
0.12
ClinPred
0.090
T
GERP RS
-0.16
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.058
gMVP
0.060

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-89789049; API