Variant chr7-112286869-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_021994.3(ZNF277):c.92-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 892,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 12)

Exomes 𝑓: 0.000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF277
NM_021994.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005583

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0170

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 7-112286869-C-T is Benign according to our data. Variant chr7-112286869-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 777631.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ZNF277	NM_021994.3 linkuse as main transcript	c.92-4C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000361822.8
ZNF277	XM_011515768.4 linkuse as main transcript	c.-139-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ZNF277	XM_017011720.3 linkuse as main transcript	c.-170-8C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF277	ENST00000361822.8 linkuse as main transcript	c.92-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_021994.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

68218

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000168

Gnomad ASJ

AF:

0.000488

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000629

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000506

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

892550

Hom.:

Cov.:

AF XY:

0.0000177

AC XY:

AN XY:

452558

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000615

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000717

Gnomad4 SAS exome

AF:

0.0000382

Gnomad4 FIN exome

AF:

0.0000233

Gnomad4 NFE exome

AF:

0.0000105

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000103

AC:

AN:

68230

Hom.:

Cov.:

AF XY:

0.0000913

AC XY:

AN XY:

32864

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000168

Gnomad4 ASJ

AF:

0.000488

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000629

Gnomad4 NFE

AF:

0.0000506

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 14, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.1

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000056

dbscSNV1_RF

Benign

0.0

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