chr19-12430157-T-A

Position:

• chr19-12430157-T-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4 BA1

The NM_005815.5(ZNF443):​c.2015A>T​(p.Ter672LeuextTer4) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,610,318 control chromosomes in the GnomAD database, including 39,560 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4913 hom., cov: 32)
  • Exomes 𝑓: 0.21 (34647 hom.)
• Consequence: ZNF443 NM_005815.5 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM4: Stoplost variant in NM_005815.5 Downstream stopcodon found after 8 codons.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF443	NM_005815.5	c.2015A>T	p.Ter672LeuextTer4	stop_lost	4/4	ENST00000301547.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF443	ENST00000301547.10	c.2015A>T	p.Ter672LeuextTer4	stop_lost	4/4	1	NM_005815.5	P1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36730 AN: 151850 Hom.: 4899 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.258

GnomAD3 exomes AF: 0.225 AC: 56081 AN: 249276 Hom.: 7302 AF XY: 0.228 AC XY: 30837 AN XY: 135240

Gnomad AFR exome AF: 0.354

Gnomad AMR exome AF: 0.285

Gnomad ASJ exome AF: 0.258

Gnomad EAS exome AF: 0.0999

Gnomad SAS exome AF: 0.363

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.226

GnomAD4 exome AF: 0.209 AC: 304584 AN: 1458350 Hom.: 34647 Cov.: 33 AF XY: 0.212 AC XY: 154131 AN XY: 725562

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.281

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.194

Gnomad4 OTH exome AF: 0.219

GnomAD4 genome AF: 0.242 AC: 36772 AN: 151968 Hom.: 4913 Cov.: 32 AF XY: 0.239 AC XY: 17728 AN XY: 74296

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.265

Alfa AF: 0.210 Hom.: 1213

Bravo AF: 0.257

ExAC AF: 0.228 AC: 27647

Asia WGS AF: 0.288 AC: 1004 AN: 3474

EpiCase AF: 0.200

EpiControl AF: 0.206

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.5
DANN	Benign	0.58
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.0043	N
MutationTaster	Benign	1.0	P
Vest4		0.0
GERP RS		-1.3

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

LitVar

Other links and lift over

dbSNP: rs28559848; hg19: chr19-12540971; COSMIC: COSV56890413; COSMIC: COSV56890413;