7-112330161-G-T

Variant names:

• chr7-112330161-G-T
• NM_021994.3:c.746G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021994.3(ZNF277):​c.746G>T​(p.Arg249Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,808 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF277 NM_021994.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.62

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF277	NM_021994.3	c.746G>T	p.Arg249Leu	missense_variant	Exon 7 of 12	ENST00000361822.8	NP_068834.2
ZNF277	XM_011515768.4	c.512G>T	p.Arg171Leu	missense_variant	Exon 7 of 12		XP_011514070.1
ZNF277	XM_017011720.3	c.392G>T	p.Arg131Leu	missense_variant	Exon 6 of 11		XP_016867209.1
ZNF277-AS1	NR_186626.1	n.147-1763C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF277	ENST00000361822.8	c.746G>T	p.Arg249Leu	missense_variant	Exon 7 of 12	1	NM_021994.3	ENSP00000354501.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460808 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726782

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;.;T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.8	M;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.033	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.80
MutPred		0.38		Loss of solvent accessibility (P = 0.0098);.;Loss of solvent accessibility (P = 0.0098);
MVP		0.65
MPC		0.52
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.51
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-111970216;