19-44428797-C-T

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF229	NM_014518.4	c.1984G>A	p.Gly662Arg	missense_variant	6/6	ENST00000614049.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF229	ENST00000614049.5	c.1984G>A	p.Gly662Arg	missense_variant	6/6	1	NM_014518.4	A2
ZNF229	ENST00000613197.4	c.1966G>A	p.Gly656Arg	missense_variant	6/6	1		P4
ZNF229	ENST00000620012.4	c.*2187G>A		3_prime_UTR_variant, NMD_transcript_variant	6/6	1
ZNF229	ENST00000591289.5	n.523-11251G>A		intron_variant, non_coding_transcript_variant		4

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

GnomAD3 exomes AF: 0.326 AC: 81535 AN: 249944 Hom.: 14398 AF XY: 0.341 AC XY: 46243 AN XY: 135540

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 SAS exome AF: 0.469

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

Gnomad4 AFR exome AF: 0.0825

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.345

Gnomad4 SAS exome AF: 0.465

Gnomad4 FIN exome AF: 0.332

Gnomad4 NFE exome AF: 0.344

Gnomad4 OTH exome AF: 0.331

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

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.303

Alfa AF: 0.329 Hom.: 20983

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 v4.3

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;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.030	P;P
PrimateAI	Uncertain	0.49	T
Sift4G	Uncertain	0.011	D;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

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