7-112206716-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.182

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]

ACMG classification

Verdict is Benign. Variant got -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 GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF277	NM_021994.3	c.-1A>G		5_prime_UTR_variant	1/12	ENST00000361822.8
ZNF277	XM_011515768.4	c.-231A>G		5_prime_UTR_variant	1/12
ZNF277	XM_017011720.3	c.-262A>G		5_prime_UTR_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF277	ENST00000361822.8	c.-1A>G		5_prime_UTR_variant	1/12	1	NM_021994.3	P1

Frequencies

GnomAD3 genomes AF: 0.00556 AC: 846 AN: 152222 Hom.: 5 Cov.: 33

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

GnomAD3 exomes AF: 0.00635 AC: 1576 AN: 248068 Hom.: 4 AF XY: 0.00688 AC XY: 927 AN XY: 134706

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 SAS exome AF: 0.00729

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.: 47 Cov.: 31 AF XY: 0.00782 AC XY: 5681 AN XY: 726718

Gnomad4 AFR exome AF: 0.00159

Gnomad4 AMR exome AF: 0.00542

Gnomad4 ASJ exome AF: 0.0140

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00733

Gnomad4 FIN exome AF: 0.00425

Gnomad4 NFE exome AF: 0.00828

Gnomad4 OTH exome AF: 0.00751

GnomAD4 genome AF: 0.00555 AC: 846 AN: 152340 Hom.: 4 Cov.: 33 AF XY: 0.00502 AC XY: 374 AN XY: 74492

Gnomad4 AFR AF: 0.00171

Gnomad4 AMR AF: 0.00647

Gnomad4 ASJ AF: 0.0181

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00600

Gnomad4 FIN AF: 0.00471

Gnomad4 NFE AF: 0.00757

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.00514 Hom.: 2

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

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

ZNF277: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	12
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs142246587; hg19: chr7-111846771;