Variant chr16-89721794-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001113525.2(ZNF276):c.154G>T(p.Gly52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,256,198 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

ZNF276
NM_001113525.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.153

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]

ZNF276 links:

Genome browser will be placed here

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=0.011316508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF276	NM_001113525.2 linkuse as main transcript	c.154G>T	p.Gly52Cys	missense_variant	1/11	ENST00000443381.7	NP_001106997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF276	ENST00000443381.7 linkuse as main transcript	c.154G>T	p.Gly52Cys	missense_variant	1/11	1	NM_001113525.2	ENSP00000415836	P2	Q8N554-1

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

162

AN:

151916

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00355

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000656

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:

0.00240

GnomAD4 exome

AF:

0.000123

AC:

136

AN:

1104176

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

526312

show subpopulations

Gnomad4 AFR exome

AF:

0.00526

Gnomad4 AMR exome

AF:

0.000492

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:

0.00000321

Gnomad4 OTH exome

AF:

0.000226

GnomAD4 genome

AF:

0.00106

AC:

161

AN:

152022

Hom.:

Cov.:

AF XY:

0.000995

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00352

Gnomad4 AMR

AF:

0.000655

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:

0.00237

Bravo

AF:

0.00134

ExAC

AF:

0.000421

AC:

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

Aug 17, 2021

The c.154G>T (p.G52C) alteration is located in exon 1 (coding exon 1) of the ZNF276 gene. This alteration results from a G to T substitution at nucleotide position 154, causing the glycine (G) at amino acid position 52 to be replaced by a cysteine (C). 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

0.26

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.31

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.28

REVEL

Benign

0.069

Sift

Benign

0.073

Sift4G

Uncertain

0.028

Polyphen

0.76

Vest4

0.13

MutPred

0.29

Gain of helix (P = 0.0022);

MVP

0.085

MPC

0.18

ClinPred

0.26

GERP RS

1.9

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.5

Varity_R

0.088

gMVP

0.21

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over