7-112318220-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_021994.3(ZNF277):c.505dup(p.Thr169AsnfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000819 in 1,613,534 control chromosomes in the GnomAD database, including 22 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0017 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (18 hom.)
• Consequence: ZNF277 NM_021994.3 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.80

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 -10 ACMG points.

• BP6: Variant 7-112318220-T-TA is Benign according to our data. Variant chr7-112318220-T-TA is described in ClinVar as [Benign]. Clinvar id is 713971.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000731 (1068/1461332) while in subpopulation AMR AF= 0.0229 (1022/44714). AF 95% confidence interval is 0.0217. There are 18 homozygotes in gnomad4_exome. There are 444 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF277	NM_021994.3	c.505dup	p.Thr169AsnfsTer12	frameshift_variant	5/12	ENST00000361822.8
ZNF277	XM_011515768.4	c.271dup	p.Thr91AsnfsTer12	frameshift_variant	5/12
ZNF277	XM_017011720.3	c.151dup	p.Thr51AsnfsTer12	frameshift_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF277	ENST00000361822.8	c.505dup	p.Thr169AsnfsTer12	frameshift_variant	5/12	1	NM_021994.3	P1

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 253 AN: 152084 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00330 AC: 828 AN: 251212 Hom.: 16 AF XY: 0.00240 AC XY: 326 AN XY: 135774

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0236

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.000731 AC: 1068 AN: 1461332 Hom.: 18 Cov.: 30 AF XY: 0.000611 AC XY: 444 AN XY: 726964

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.0229

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.000563

GnomAD4 genome AF: 0.00166 AC: 253 AN: 152202 Hom.: 4 Cov.: 32 AF XY: 0.00187 AC XY: 139 AN XY: 74418

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.0159

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000253 Hom.: 1

Bravo AF: 0.00266

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 18, 2017

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs527469015; hg19: chr7-111958275;