rs11539696

Variant names:

• chr7-112340952-G-A
• rs11539696
• NM_021994.3:c.1090G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/22 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 the same amino acid substitution has been previously reported as Likely benign in 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)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZNF277	NM_021994.3	c.1090G>A	p.Val364Met	missense_variant	Exon 11 of 12	ENST00000361822.8	NP_068834.2
ZNF277	XM_011515768.4	c.856G>A	p.Val286Met	missense_variant	Exon 11 of 12		XP_011514070.1
ZNF277	XM_017011720.3	c.736G>A	p.Val246Met	missense_variant	Exon 10 of 11		XP_016867209.1
ZNF277-AS1	NR_186626.1	n.146+103C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF277	ENST00000361822.8	c.1090G>A	p.Val364Met	missense_variant	Exon 11 of 12	1	NM_021994.3	ENSP00000354501.3

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

GnomAD2 exomes AF: 0.0545 AC: 13635 AN: 250036 AF XY: 0.0563

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 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 AC: 1497 AN: 33440

Gnomad4 AMR exome AF: 0.0361 AC: 1606 AN: 44502

Gnomad4 ASJ exome AF: 0.101 AC: 2646 AN: 26118

Gnomad4 EAS exome AF: 0.0350 AC: 1388 AN: 39668

Gnomad4 SAS exome AF: 0.0494 AC: 4237 AN: 85738

Gnomad4 FIN exome AF: 0.0539 AC: 2878 AN: 53412

Gnomad4 NFE exome AF: 0.0593 AC: 65907 AN: 1111488

Gnomad4 Remaining exome AF: 0.0634 AC: 3829 AN: 60356

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 AC: 0.047806 AN: 0.047806

Gnomad4 AMR AF: 0.0494 AC: 0.0494441 AN: 0.0494441

Gnomad4 ASJ AF: 0.0956 AC: 0.0956221 AN: 0.0956221

Gnomad4 EAS AF: 0.0319 AC: 0.0318533 AN: 0.0318533

Gnomad4 SAS AF: 0.0497 AC: 0.0497306 AN: 0.0497306

Gnomad4 FIN AF: 0.0524 AC: 0.0524133 AN: 0.0524133

Gnomad4 NFE AF: 0.0608 AC: 0.0607892 AN: 0.0607892

Gnomad4 OTH AF: 0.0696 AC: 0.0696023 AN: 0.0696023

Alfa AF: 0.0619 Hom.: 1217

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
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
Mutation Taster		=95/5	polymorphism (auto)

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;