3-44446720-C-T

Variant names:

• chr3-44446720-C-T
• NM_181489.6:c.2951G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_181489.6(ZNF445):​c.2951G>A​(p.Gly984Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF445 NM_181489.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89
• Publications: 0 publications found

Genes affected

ZNF445 (HGNC:21018): (zinc finger protein 445) Enables double-stranded methylated DNA binding activity. Involved in maintenance of DNA methylation and regulation of genetic imprinting. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181489.6. 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
	ZNF445	NM_181489.6	MANE Select	c.2951G>A	p.Gly984Glu	missense	Exon 8 of 8	NP_852466.1	P59923
	ZNF445	NM_001369454.1		c.2915G>A	p.Gly972Glu	missense	Exon 7 of 7	NP_001356383.1	B7ZKX2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF445	ENST00000396077.8	TSL:1 MANE Select	c.2951G>A	p.Gly984Glu	missense	Exon 8 of 8	ENSP00000379387.2	P59923
	ZNF445	ENST00000425708.6	TSL:1	c.2951G>A	p.Gly984Glu	missense	Exon 6 of 6	ENSP00000413073.2	P59923
	ZNF445	ENST00000924004.1		c.2951G>A	p.Gly984Glu	missense	Exon 7 of 7	ENSP00000594063.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

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	Uncertain	0.55
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.80	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.9
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.17
Sift	Benign	0.066	T
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.51
MutPred		0.63		Loss of MoRF binding (P = 0.0253)
MVP		0.54
MPC		1.0
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.26
gMVP		0.22
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr3-44488212;