NM_005815.5:c.1961G>A

Variant names:

• chr19-12430211-C-T
• rs756517794
• NM_005815.5:c.1961G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005815.5(ZNF443):​c.1961G>A​(p.Cys654Tyr) variant causes a missense 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF443 NM_005815.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50
• Publications: 0 publications found

Genes affected

ZNF443 (HGNC:20878): (zinc finger protein 443) Zinc finger proteins (ZNFs) bind DNA and, through this binding, regulate gene transcription. Most ZNFs contain conserved C2H2 motifs and are classified as Kruppel-type zinc fingers. For a general description of these proteins, see ZNF91 (MIM 603971).[supplied by OMIM, Jul 2002]

ENSG00000268870 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.835

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005815.5. 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
	ZNF443	NM_005815.5	MANE Select	c.1961G>A	p.Cys654Tyr	missense	Exon 4 of 4	NP_005806.3	Q9Y2A4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF443	ENST00000301547.10	TSL:1 MANE Select	c.1961G>A	p.Cys654Tyr	missense	Exon 4 of 4	ENSP00000301547.5	Q9Y2A4
	ENSG00000268870	ENST00000595562.1	TSL:4	c.3+10701G>A		intron	N/A	ENSP00000471613.1	M0R135

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.45
BayesDel_addAF	Benign	0.0040	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	17
DANN	Benign	0.81
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0040	T
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		1.5
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.23
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.98	D
Vest4		0.21
MutPred		0.91		Loss of methylation at K656 (P = 0.0662)
MVP		0.69
MPC		0.11
ClinPred		0.65	D
GERP RS		-0.95
Varity_R		0.28
gMVP		0.10
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs756517794; hg19: chr19-12541025;