Variant rs11539696 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021994.3(ZNF277):c.1090G>A(p.Val364Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 1,612,724 control chromosomes in the GnomAD database, including 2,958 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.056 ( 279 hom., cov: 32)

Exomes 𝑓: 0.058 ( 2679 hom. )

Consequence

ZNF277
NM_021994.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.719

Variant links:

Genes affected

ZNF277 (HGNC:13070): (zinc finger protein 277) Predicted to enable RNA polymerase II cis-regulatory region sequence-specific DNA binding activity and metal ion binding activity. Predicted to act upstream of or within cellular response to hydrogen peroxide and regulation of cellular senescence. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF277 links:

ZNF277-AS1 (HGNC:55828): (ZNF277 antisense RNA 1)

ZNF277-AS1 links:

LOC124901728 (HGNC:):

LOC124901728 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017106831).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF277	NM_021994.3 linkuse as main transcript	c.1090G>A	p.Val364Met	missense_variant	11/12	ENST00000361822.8	NP_068834.2
ZNF277	XM_011515768.4 linkuse as main transcript	c.856G>A	p.Val286Met	missense_variant	11/12		XP_011514070.1
ZNF277	XM_017011720.3 linkuse as main transcript	c.736G>A	p.Val246Met	missense_variant	10/11		XP_016867209.1
LOC124901728	XR_007060480.1 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF277	ENST00000361822.8 linkuse as main transcript	c.1090G>A	p.Val364Met	missense_variant	11/12	1	NM_021994.3	ENSP00000354501	P1
ZNF277-AS1	ENST00000431064.1 linkuse as main transcript	n.352-12554C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0558

AC:

8488

AN:

152116

Hom.:

282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0478

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.0495

Gnomad ASJ

AF:

0.0956

Gnomad EAS

AF:

0.0320

Gnomad SAS

AF:

0.0499

Gnomad FIN

AF:

0.0524

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.0608

Gnomad OTH

AF:

0.0703

GnomAD3 exomes

AF:

0.0545

AC:

13635

AN:

250036

Hom.:

475

AF XY:

0.0563

AC XY:

7605

AN XY:

135164

show subpopulations

Gnomad AFR exome

AF:

0.0455

Gnomad AMR exome

AF:

0.0333

Gnomad ASJ exome

AF:

0.0998

Gnomad EAS exome

AF:

0.0285

Gnomad SAS exome

AF:

0.0501

Gnomad FIN exome

AF:

0.0560

Gnomad NFE exome

AF:

0.0624

Gnomad OTH exome

AF:

0.0707

GnomAD4 exome

AF:

0.0580

AC:

84733

AN:

1460488

Hom.:

2679

Cov.:

AF XY:

0.0581

AC XY:

42185

AN XY:

726480

show subpopulations

Gnomad4 AFR exome

AF:

0.0448

Gnomad4 AMR exome

AF:

0.0361

Gnomad4 ASJ exome

AF:

0.101

Gnomad4 EAS exome

AF:

0.0350

Gnomad4 SAS exome

AF:

0.0494

Gnomad4 FIN exome

AF:

0.0539

Gnomad4 NFE exome

AF:

0.0593

Gnomad4 OTH exome

AF:

0.0634

GnomAD4 genome

AF:

0.0558

AC:

8488

AN:

152236

Hom.:

279

Cov.:

AF XY:

0.0553

AC XY:

4115

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0478

Gnomad4 AMR

AF:

0.0494

Gnomad4 ASJ

AF:

0.0956

Gnomad4 EAS

AF:

0.0319

Gnomad4 SAS

AF:

0.0497

Gnomad4 FIN

AF:

0.0524

Gnomad4 NFE

AF:

0.0608

Gnomad4 OTH

AF:

0.0696

Alfa

AF:

0.0646

Hom.:

709

Bravo

AF:

0.0564

TwinsUK

AF:

0.0612

AC:

227

ALSPAC

AF:

0.0560

AC:

216

ESP6500AA

AF:

0.0427

AC:

188

ESP6500EA

AF:

0.0670

AC:

576

ExAC

AF:

0.0549

AC:

6672

Asia WGS

AF:

0.0550

AC:

190

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0018

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.050

REVEL

Benign

0.024

Sift

Benign

0.11

Sift4G

Benign

0.097

Polyphen

0.30

Vest4

0.048

MPC

0.12

ClinPred

0.0040

GERP RS

-0.11

Varity_R

0.032

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over