rs201172958

Variant names:

• chr7-112330157-C-T
• rs201172958
• NM_021994.3:c.742C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021994.3(ZNF277):​c.742C>T​(p.His248Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ZNF277 NM_021994.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.61
• Publications: 0 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.909

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.742C>T	p.His248Tyr	missense	Exon 7 of 12	NP_068834.2	Q9NRM2
	ZNF277-AS1	NR_186626.1		n.147-1759G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF277	ENST00000361822.8	TSL:1 MANE Select	c.742C>T	p.His248Tyr	missense	Exon 7 of 12	ENSP00000354501.3	Q9NRM2
	ZNF277	ENST00000450657.1	TSL:1	c.742C>T	p.His248Tyr	missense	Exon 7 of 7	ENSP00000402292.1	G5E9M4
	ZNF277	ENST00000361946.8	TSL:1	n.*585C>T		non_coding_transcript_exon	Exon 7 of 12	ENSP00000355043.4	E7EW13

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250646 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460732 Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6 AN XY: 726738

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111494

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74332

African (AFR) AF: 0.00 AC: 0 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.99
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Pathogenic	3.7	H
PhyloP100		7.6
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.78		Loss of solvent accessibility (P = 0.0172)
MVP		0.99
MPC		0.58
ClinPred		1.0	D
GERP RS		6.2
Varity_R		0.84
gMVP		0.73
Mutation Taster		=8/92	disease causing

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: rs201172958; hg19: chr7-111970212;