19-44428797-C-T

Variant names:

• chr19-44428797-C-T
• rs1434579
• NM_014518.4:c.1984G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014518.4(ZNF229):​c.1984G>A​(p.Gly662Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,613,830 control chromosomes in the GnomAD database, including 94,425 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 0.27 (6667 hom., cov: 32)
  • Exomes 𝑓: 0.34 (87758 hom.)
• Consequence: ZNF229 NM_014518.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72
• Publications: 41 publications found

Genes affected

ZNF229 (HGNC:13022): (zinc finger protein 229) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF229 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000267188 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.544326E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014518.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF229	NM_014518.4	MANE Select	c.1984G>A	p.Gly662Arg	missense	Exon 6 of 6	NP_055333.3
	ZNF229	NM_001278510.3		c.1966G>A	p.Gly656Arg	missense	Exon 6 of 6	NP_001265439.2
	ZNF229	NR_103551.3		n.2868G>A		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF229	ENST00000614049.5	TSL:1 MANE Select	c.1984G>A	p.Gly662Arg	missense	Exon 6 of 6	ENSP00000479884.1
	ZNF229	ENST00000613197.4	TSL:1	c.1966G>A	p.Gly656Arg	missense	Exon 6 of 6	ENSP00000479807.1
	ZNF229	ENST00000620012.4	TSL:1	n.*2187G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000483138.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40929 AN: 151846 Hom.: 6670 Cov.: 32

Gnomad AFR AF: 0.0942

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.303

GnomAD2 exomes AF: 0.326 AC: 81535 AN: 249944 AF XY: 0.341

Gnomad AFR exome AF: 0.0884

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.333

Gnomad EAS exome AF: 0.331

Gnomad FIN exome AF: 0.334

Gnomad NFE exome AF: 0.338

Gnomad OTH exome AF: 0.335

GnomAD4 exome AF: 0.341 AC: 498794 AN: 1461866 Hom.: 87758 Cov.: 83 AF XY: 0.347 AC XY: 252029 AN XY: 727236

African (AFR) AF: 0.0825 AC: 2763 AN: 33476

American (AMR) AF: 0.263 AC: 11770 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 8379 AN: 26136

East Asian (EAS) AF: 0.345 AC: 13682 AN: 39686

South Asian (SAS) AF: 0.465 AC: 40071 AN: 86258

European-Finnish (FIN) AF: 0.332 AC: 17757 AN: 53418

Middle Eastern (MID) AF: 0.317 AC: 1830 AN: 5768

European-Non Finnish (NFE) AF: 0.344 AC: 382534 AN: 1112004

Other (OTH) AF: 0.331 AC: 20008 AN: 60396

GnomAD4 genome AF: 0.269 AC: 40930 AN: 151964 Hom.: 6667 Cov.: 32 AF XY: 0.272 AC XY: 20236 AN XY: 74284

African (AFR) AF: 0.0941 AC: 3899 AN: 41442

American (AMR) AF: 0.275 AC: 4204 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1148 AN: 3464

East Asian (EAS) AF: 0.330 AC: 1697 AN: 5140

South Asian (SAS) AF: 0.467 AC: 2249 AN: 4818

European-Finnish (FIN) AF: 0.342 AC: 3615 AN: 10558

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22977 AN: 67958

Other (OTH) AF: 0.303 AC: 639 AN: 2108

Alfa AF: 0.318 Hom.: 27596

Bravo AF: 0.254

TwinsUK AF: 0.342 AC: 1267

ALSPAC AF: 0.331 AC: 1276

ESP6500AA AF: 0.0911 AC: 393

ESP6500EA AF: 0.341 AC: 2912

ExAC AF: 0.324 AC: 39230

Asia WGS AF: 0.353 AC: 1228 AN: 3478

EpiCase AF: 0.354

EpiControl AF: 0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	0.083
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.85	T
MetaRNN	Benign	0.00085	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.7
PrimateAI	Uncertain	0.49	T
Sift4G	Uncertain	0.011	D
Vest4		0.091
MutPred		0.64		Gain of MoRF binding (P = 0.0186)
ClinPred		0.037	T
GERP RS		3.5
gMVP		0.053
Mutation Taster		=97/3	polymorphism (auto)

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: rs1434579; hg19: chr19-44932972; COSMIC: COSV52160616; COSMIC: COSV52160616;