rs200427541

Variant names:

• chr19-12430664-G-A
• rs200427541
• NM_005815.5:c.1508C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005815.5(ZNF443):​c.1508C>T​(p.Pro503Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000563 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00058 (0 hom.)
• Consequence: ZNF443 NM_005815.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.93
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13657299).

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.1508C>T	p.Pro503Leu	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.1508C>T	p.Pro503Leu	missense	Exon 4 of 4	ENSP00000301547.5	Q9Y2A4
	ENSG00000268870	ENST00000595562.1	TSL:4	c.3+10248C>T		intron	N/A	ENSP00000471613.1	M0R135

Frequencies

GnomAD3 genomes AF: 0.000348 AC: 53 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000235 AC: 59 AN: 251164 AF XY: 0.000273

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000449

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000585 AC: 855 AN: 1461798 Hom.: 0 Cov.: 49 AF XY: 0.000597 AC XY: 434 AN XY: 727188

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.000134 AC: 6 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000729 AC: 811 AN: 1111958

Other (OTH) AF: 0.000580 AC: 35 AN: 60392

GnomAD4 genome AF: 0.000348 AC: 53 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74320

African (AFR) AF: 0.000169 AC: 7 AN: 41420

American (AMR) AF: 0.000196 AC: 3 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000632 AC: 43 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000410 Hom.: 0

Bravo AF: 0.000366

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000255 AC: 31

EpiCase AF: 0.000545

EpiControl AF: 0.000533

ClinVar

ClinVar submissions as Germline

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	Benign	0.28
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.050	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.9
PrimateAI	Benign	0.33	T
PROVEAN	Pathogenic	-7.7	D
REVEL	Benign	0.19
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.020	D
Polyphen		0.51	P
Vest4		0.23
MVP		0.47
MPC		0.062
ClinPred		0.81	D
GERP RS		1.3
Varity_R		0.12
gMVP		0.0096
Mutation Taster		=96/4	polymorphism

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

dbSNP: rs200427541; hg19: chr19-12541478; COSMIC: COSV99041752; COSMIC: COSV99041752;