rs11539696

chr7-112340952-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021994.3(ZNF277):c.1090G>A(p.Val364Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0578 in 1,612,724 control chromosomes in the GnomAD database, including 2,958 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.056 (279 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2679 hom.)
• Consequence: ZNF277 NM_021994.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719

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-AS1 (HGNC:55828): (ZNF277 antisense RNA 1)

LOC124901728 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017106831).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF277	NM_021994.3	c.1090G>A	p.Val364Met	missense_variant	11/12	ENST00000361822.8
ZNF277	XM_011515768.4	c.856G>A	p.Val286Met	missense_variant	11/12
ZNF277	XM_017011720.3	c.736G>A	p.Val246Met	missense_variant	10/11
LOC124901728	XR_007060480.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF277	ENST00000361822.8	c.1090G>A	p.Val364Met	missense_variant	11/12	1	NM_021994.3	P1
ZNF277-AS1	ENST00000431064.1	n.352-12554C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8488 AN: 152116 Hom.: 282 Cov.: 32

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0495

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.0320

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.0524

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0608

Gnomad OTH AF: 0.0703

GnomAD3 exomes AF: 0.0545 AC: 13635 AN: 250036 Hom.: 475 AF XY: 0.0563 AC XY: 7605 AN XY: 135164

Gnomad AFR exome AF: 0.0455

Gnomad AMR exome AF: 0.0333

Gnomad ASJ exome AF: 0.0998

Gnomad EAS exome AF: 0.0285

Gnomad SAS exome AF: 0.0501

Gnomad FIN exome AF: 0.0560

Gnomad NFE exome AF: 0.0624

Gnomad OTH exome AF: 0.0707

GnomAD4 exome AF: 0.0580 AC: 84733 AN: 1460488 Hom.: 2679 Cov.: 31 AF XY: 0.0581 AC XY: 42185 AN XY: 726480

Gnomad4 AFR exome AF: 0.0448

Gnomad4 AMR exome AF: 0.0361

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.0350

Gnomad4 SAS exome AF: 0.0494

Gnomad4 FIN exome AF: 0.0539

Gnomad4 NFE exome AF: 0.0593

Gnomad4 OTH exome AF: 0.0634

GnomAD4 genome AF: 0.0558 AC: 8488 AN: 152236 Hom.: 279 Cov.: 32 AF XY: 0.0553 AC XY: 4115 AN XY: 74432

Gnomad4 AFR AF: 0.0478

Gnomad4 AMR AF: 0.0494

Gnomad4 ASJ AF: 0.0956

Gnomad4 EAS AF: 0.0319

Gnomad4 SAS AF: 0.0497

Gnomad4 FIN AF: 0.0524

Gnomad4 NFE AF: 0.0608

Gnomad4 OTH AF: 0.0696

Alfa AF: 0.0646 Hom.: 709

Bravo AF: 0.0564

TwinsUK AF: 0.0612 AC: 227

ALSPAC AF: 0.0560 AC: 216

ESP6500AA AF: 0.0427 AC: 188

ESP6500EA AF: 0.0670 AC: 576

ExAC AF: 0.0549 AC: 6672

Asia WGS AF: 0.0550 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	12
Dann	Benign	0.97
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.024
Sift	Benign	0.11	T
Sift4G	Benign	0.097	T
Polyphen		0.30	B
Vest4		0.048
MPC		0.12
ClinPred		0.0040	T
GERP RS		-0.11
Varity_R		0.032
gMVP		0.21

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: rs11539696; hg19: chr7-111981007; COSMIC: COSV62464500; COSMIC: COSV62464500;