Genetic Variant ZNF277:c.-1A>G (chr7-112206716-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_021994.3(ZNF277):c.-1A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00747 in 1,613,132 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 47 hom. )

Consequence

ZNF277
NM_021994.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.182

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 7-112206716-A-G is Benign according to our data. Variant chr7-112206716-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2657946.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ZNF277	NM_021994.3 link	c.-1A>G	5_prime_UTR_variant	Exon 1 of 12	ENST00000361822.8	NP_068834.2	Q9NRM2
ZNF277	XM_011515768.4 link	c.-231A>G	5_prime_UTR_variant	Exon 1 of 12		XP_011514070.1
ZNF277	XM_017011720.3 link	c.-262A>G	5_prime_UTR_variant	Exon 1 of 11		XP_016867209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF277	ENST00000361822 link	c.-1A>G		5_prime_UTR_variant	Exon 1 of 12	1	NM_021994.3	ENSP00000354501.3		Q9NRM2

Frequencies

GnomAD3 genomes

AF:

0.00556

AC:

846

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00648

Gnomad ASJ

AF:

0.0181

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.00471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00754

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00635

AC:

1576

AN:

248068

AF XY:

0.00688

show subpopulations

Gnomad AFR exome

AF:

0.00165

Gnomad AMR exome

AF:

0.00454

Gnomad ASJ exome

AF:

0.0138

Gnomad EAS exome

AF:

0.0000549

Gnomad FIN exome

AF:

0.00366

Gnomad NFE exome

AF:

0.00815

Gnomad OTH exome

AF:

0.00682

GnomAD4 exome

AF:

0.00767

AC:

11198

AN:

1460792

Hom.:

Cov.:

AF XY:

0.00782

AC XY:

5681

AN XY:

726718

show subpopulations

Gnomad4 AFR exome

AF:

0.00159

AC:

AN:

33418

Gnomad4 AMR exome

AF:

0.00542

AC:

242

AN:

44658

Gnomad4 ASJ exome

AF:

0.0140

AC:

365

AN:

26096

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39610

Gnomad4 SAS exome

AF:

0.00733

AC:

632

AN:

86200

Gnomad4 FIN exome

AF:

0.00425

AC:

226

AN:

53156

Gnomad4 NFE exome

AF:

0.00828

AC:

9199

AN:

1111582

Gnomad4 Remaining exome

AF:

0.00751

AC:

453

AN:

60336

Heterozygous variant carriers

571

1142

1712

2283

2854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.00555

AC:

846

AN:

152340

Hom.:

Cov.:

AF XY:

0.00502

AC XY:

374

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00171

AC:

0.00170739

AN:

0.00170739

Gnomad4 AMR

AF:

0.00647

AC:

0.00646721

AN:

0.00646721

Gnomad4 ASJ

AF:

0.0181

AC:

0.0181452

AN:

0.0181452

Gnomad4 EAS

AF:

0.000193

AC:

0.000193424

AN:

0.000193424

Gnomad4 SAS

AF:

0.00600

AC:

0.00600166

AN:

0.00600166

Gnomad4 FIN

AF:

0.00471

AC:

0.00470721

AN:

0.00470721

Gnomad4 NFE

AF:

0.00757

AC:

0.00756997

AN:

0.00756997

Gnomad4 OTH

AF:

0.00804

AC:

0.00804163

AN:

0.00804163

Heterozygous variant carriers

143

190

238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<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:

0.00514

Hom.:

Bravo

AF:

0.00576

EpiCase

AF:

0.00812

EpiControl

AF:

0.00849

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ZNF277: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=300/0

polymorphism

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