7-112286869-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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

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 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	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF277	NM_021994.3	c.92-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000361822.8
ZNF277	XM_011515768.4	c.-139-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ZNF277	XM_017011720.3	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	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: 7 AN: 68218 Hom.: 0 Cov.: 12 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: 14 AN: 892550 Hom.: 0 Cov.: 30 AF XY: 0.0000177 AC XY: 8 AN XY: 452558

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: 7 AN: 68230 Hom.: 0 Cov.: 12 AF XY: 0.0000913 AC XY: 3 AN XY: 32864

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

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

Other links and lift over

dbSNP: rs1449984619; hg19: chr7-111926924;