dbSNP rs1452851644: ZNF276:p.Gly55Ala (chr16-89721804-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001113525.2(ZNF276):c.164G>C(p.Gly55Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000888 in 1,238,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000092 ( 0 hom. )

Consequence

ZNF276
NM_001113525.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.251

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]

ZNF276 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057816386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF276	NM_001113525.2 link	c.164G>C	p.Gly55Ala	missense_variant	Exon 1 of 11	ENST00000443381.7	NP_001106997.1	Q8N554-1I6L9I3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF276	ENST00000443381.7 link	c.164G>C	p.Gly55Ala	missense_variant	Exon 1 of 11	1	NM_001113525.2	ENSP00000415836.2		Q8N554-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151870

Hom.:

Cov.:

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000921

AC:

AN:

1086218

Hom.:

Cov.:

AF XY:

0.00000776

AC XY:

AN XY:

515180

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22488

American (AMR)

AF:

0.00

AC:

AN:

8030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14044

East Asian (EAS)

AF:

0.00

AC:

AN:

25610

South Asian (SAS)

AF:

0.00

AC:

AN:

24010

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2898

European-Non Finnish (NFE)

AF:

0.0000108

AC:

AN:

923760

Other (OTH)

AF:

0.00

AC:

AN:

43484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151870

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41404

American (AMR)

AF:

0.00

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67934

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 23, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.164G>C (p.G55A) alteration is located in exon 1 (coding exon 1) of the ZNF276 gene. This alteration results from a G to C substitution at nucleotide position 164, causing the glycine (G) at amino acid position 55 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

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

6.2

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.048

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.44

M_CAP

Benign

0.024

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

PhyloP100

-0.25

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.0

REVEL

Benign

0.0090

Sift

Benign

0.30

Sift4G

Benign

0.66

Polyphen

0.0020

Vest4

0.069

MutPred

0.15

Gain of MoRF binding (P = 0.1239);

MVP

0.014

MPC

0.073

ClinPred

0.052

GERP RS

-0.75

PromoterAI

0.0016

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.9

Varity_R

0.037

gMVP

0.070

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs1452851644

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over