NM_005815.5:c.1343C>G

Variant names:

• chr19-12430829-G-C
• NM_005815.5:c.1343C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005815.5(ZNF443):​c.1343C>G​(p.Pro448Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF443 NM_005815.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.913

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2687842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF443	NM_005815.5	c.1343C>G	p.Pro448Arg	missense_variant	Exon 4 of 4	ENST00000301547.10	NP_005806.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF443	ENST00000301547.10	c.1343C>G	p.Pro448Arg	missense_variant	Exon 4 of 4	1	NM_005815.5	ENSP00000301547.5
ENSG00000268870	ENST00000595562.1	c.3+10083C>G		intron_variant	Intron 1 of 3	4		ENSP00000471613.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461802 Hom.: 0 Cov.: 94 AF XY: 0.00000138 AC XY: 1 AN XY: 727184

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Benign	0.048
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.051	T
M_CAP	Benign	0.00048	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-7.4	D
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.21
MutPred		0.57		Gain of MoRF binding (P = 0.0018);
MVP		0.43
MPC		0.26
ClinPred		0.96	D
GERP RS		1.4
Varity_R		0.40
gMVP		0.014

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: chr19-12541643;