Genetic Variant NM_021994.3:c.1090G>A (chr7-112340952-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

15 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF277	NM_021994.3 link	c.1090G>A	p.Val364Met	missense_variant	Exon 11 of 12	ENST00000361822.8	NP_068834.2	Q9NRM2
ZNF277	XM_011515768.4 link	c.856G>A	p.Val286Met	missense_variant	Exon 11 of 12		XP_011514070.1
ZNF277	XM_017011720.3 link	c.736G>A	p.Val246Met	missense_variant	Exon 10 of 11		XP_016867209.1
ZNF277-AS1	NR_186626.1 link	n.146+103C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF277	ENST00000361822.8 link	c.1090G>A	p.Val364Met	missense_variant	Exon 11 of 12	1	NM_021994.3	ENSP00000354501.3		Q9NRM2

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

GnomAD2 exomes

AF:

0.0545

AC:

13635

AN:

250036

AF XY:

0.0563

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 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

African (AFR)

AF:

0.0448

AC:

1497

AN:

33440

American (AMR)

AF:

0.0361

AC:

1606

AN:

44502

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

2646

AN:

26118

East Asian (EAS)

AF:

0.0350

AC:

1388

AN:

39668

South Asian (SAS)

AF:

0.0494

AC:

4237

AN:

85738

European-Finnish (FIN)

AF:

0.0539

AC:

2878

AN:

53412

Middle Eastern (MID)

AF:

0.129

AC:

745

AN:

5766

European-Non Finnish (NFE)

AF:

0.0593

AC:

65907

AN:

1111488

Other (OTH)

AF:

0.0634

AC:

3829

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

4140

8281

12421

16562

20702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2426

4852

7278

9704

12130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0558

AC:

8488

AN:

152236

Hom.:

279

Cov.:

AF XY:

0.0553

AC XY:

4115

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0478

AC:

1985

AN:

41522

American (AMR)

AF:

0.0494

AC:

756

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0956

AC:

332

AN:

3472

East Asian (EAS)

AF:

0.0319

AC:

165

AN:

5180

South Asian (SAS)

AF:

0.0497

AC:

240

AN:

4826

European-Finnish (FIN)

AF:

0.0524

AC:

556

AN:

10608

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0608

AC:

4135

AN:

68022

Other (OTH)

AF:

0.0696

AC:

147

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

410

820

1229

1639

2049

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0619

Hom.:

1217

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

(source)

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

PhyloP100

0.72

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

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over