7-112286866-A-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_021994.3(ZNF277):c.92-7A>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 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 0.052 (0 hom., cov: 0)
  • Exomes 𝑓: 0.011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF277 NM_021994.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002733
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.181

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-112286866-A-T is Benign according to our data. Variant chr7-112286866-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 777630.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.92-7A>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000361822.8
ZNF277	XM_011515768.4	c.-139-11A>T		splice_polypyrimidine_tract_variant, intron_variant
ZNF277	XM_017011720.3	c.-170-11A>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF277	ENST00000361822.8	c.92-7A>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_021994.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2396 AN: 45916 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0556

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0373

Gnomad EAS AF: 0.0238

Gnomad SAS AF: 0.0390

Gnomad FIN AF: 0.0281

Gnomad MID AF: 0.0189

Gnomad NFE AF: 0.0381

Gnomad OTH AF: 0.0520

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0105 AC: 8548 AN: 812888 Hom.: 0 Cov.: 29 AF XY: 0.0120 AC XY: 4872 AN XY: 407038

Gnomad4 AFR exome AF: 0.0235

Gnomad4 AMR exome AF: 0.0286

Gnomad4 ASJ exome AF: 0.0170

Gnomad4 EAS exome AF: 0.0161

Gnomad4 SAS exome AF: 0.0551

Gnomad4 FIN exome AF: 0.0238

Gnomad4 NFE exome AF: 0.00583

Gnomad4 OTH exome AF: 0.00868

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0524 AC: 2406 AN: 45932 Hom.: 0 Cov.: 0 AF XY: 0.0531 AC XY: 1183 AN XY: 22286

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.0352

Gnomad4 ASJ AF: 0.0373

Gnomad4 EAS AF: 0.0233

Gnomad4 SAS AF: 0.0398

Gnomad4 FIN AF: 0.0281

Gnomad4 NFE AF: 0.0381

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0493 Hom.: 0

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.4
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000027
dbscSNV1_RF	Benign	0.068
SpliceAI score (max)		0.10		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: rs1040348360; hg19: chr7-111926921;