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16-89722801-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001113525.2(ZNF276):c.476C>T(p.Ala159Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,453,918 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZNF276
NM_001113525.2 missense

Scores

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0520
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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.020112932).
BP6
Variant 16-89722801-C-T is Benign according to our data. Variant chr16-89722801-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3194831.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF276NM_001113525.2 linkuse as main transcriptc.476C>T p.Ala159Val missense_variant 2/11 ENST00000443381.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF276ENST00000443381.7 linkuse as main transcriptc.476C>T p.Ala159Val missense_variant 2/111 NM_001113525.2 P2Q8N554-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD3 exomes
AF:
0.0000163
AC:
4
AN:
245034
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
133350
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000999
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000413
AC:
6
AN:
1453918
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
723546
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsOct 20, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.82
Cadd
Benign
2.2
Dann
Benign
0.71
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.061
N
LIST_S2
Benign
0.46
T;T;T
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.020
T;T;T
MetaSVM
Benign
-0.92
T
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.070
N;N;N
REVEL
Benign
0.032
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
B;.;B
Vest4
0.20
MutPred
0.47
.;.;Gain of loop (P = 0.0166);
MVP
0.014
MPC
0.067
ClinPred
0.019
T
GERP RS
-0.95
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.032
gMVP
0.065

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: rs780008254; hg19: chr16-89789209; API