chr3-44446868-G-A

Variant names:

• chr3-44446868-G-A
• NM_181489.6:c.2803C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_181489.6(ZNF445):​c.2803C>T​(p.Gln935*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF445 NM_181489.6 stop_gained
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.32
• Publications: 1 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 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0946 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• 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.2803C>T	p.Gln935*	stop_gained	Exon 8 of 8	NP_852466.1	P59923
	ZNF445	NM_001369454.1		c.2767C>T	p.Gln923*	stop_gained	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.2803C>T	p.Gln935*	stop_gained	Exon 8 of 8	ENSP00000379387.2	P59923
	ZNF445	ENST00000425708.6	TSL:1	c.2803C>T	p.Gln935*	stop_gained	Exon 6 of 6	ENSP00000413073.2	P59923
	ZNF445	ENST00000924004.1		c.2803C>T	p.Gln935*	stop_gained	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: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
CADD	Pathogenic	33
DANN	Uncertain	1.0
Eigen	Uncertain	0.47
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.024	N
PhyloP100		1.3
Vest4		0.045
GERP RS		4.3
Mutation Taster		=81/119	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

hg19: chr3-44488360;