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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 15 publications found

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021994.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF277	NM_021994.3	MANE Select	c.1090G>A	p.Val364Met	missense	Exon 11 of 12	NP_068834.2	Q9NRM2
	ZNF277-AS1	NR_186626.1		n.146+103C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF277	ENST00000361822.8	TSL:1 MANE Select	c.1090G>A	p.Val364Met	missense	Exon 11 of 12	ENSP00000354501.3	Q9NRM2
	ZNF277	ENST00000361946.8	TSL:1	n.*933G>A		non_coding_transcript_exon	Exon 11 of 12	ENSP00000355043.4	E7EW13
	ZNF277	ENST00000361946.8	TSL:1	n.*933G>A		3_prime_UTR	Exon 11 of 12	ENSP00000355043.4	E7EW13

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

African (AFR) AF: 0.0448 AC: 1497 AN: 33440

American (AMR) AF: 0.0361 AC: 1606 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 2646 AN: 26118

East Asian (EAS) AF: 0.0350 AC: 1388 AN: 39668

South Asian (SAS) AF: 0.0494 AC: 4237 AN: 85738

European-Finnish (FIN) AF: 0.0539 AC: 2878 AN: 53412

Middle Eastern (MID) AF: 0.129 AC: 745 AN: 5766

European-Non Finnish (NFE) AF: 0.0593 AC: 65907 AN: 1111488

Other (OTH) 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

African (AFR) AF: 0.0478 AC: 1985 AN: 41522

American (AMR) AF: 0.0494 AC: 756 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 332 AN: 3472

East Asian (EAS) AF: 0.0319 AC: 165 AN: 5180

South Asian (SAS) AF: 0.0497 AC: 240 AN: 4826

European-Finnish (FIN) AF: 0.0524 AC: 556 AN: 10608

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0608 AC: 4135 AN: 68022

Other (OTH) AF: 0.0696 AC: 147 AN: 2112

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 v4.9

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
PhyloP100		0.72
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

Other links and lift over

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