chr19-36997153-T-G

Variant names:

• chr19-36997153-T-G
• rs10405238
• ENST00000444991.6:c.1462T>G

Variant summary

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

The NM_001204838.2(ZNF568):​c.1462T>G​(p.Tyr488Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,586,450 control chromosomes in the GnomAD database, including 22,265 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 0.18 (2431 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19834 hom.)
• Consequence: ZNF568 NM_001204838.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.62
• Publications: 16 publications found

Genes affected

ZNF568 (HGNC:25392): (zinc finger protein 568) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in embryonic placenta morphogenesis and negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000291239 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0061773956).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001204838.2. 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
	ZNF568	NM_001204838.2		c.1462T>G	p.Tyr488Asp	missense	Exon 10 of 10	NP_001191767.1	C9JLX5
	ZNF568	NM_001204839.2		c.1270T>G	p.Tyr424Asp	missense	Exon 9 of 9	NP_001191768.1	Q3ZCX4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF568	ENST00000444991.6	TSL:1	c.1462T>G	p.Tyr488Asp	missense	Exon 10 of 10	ENSP00000389794.2	C9JLX5
	ENSG00000291239	ENST00000706165.1		c.1462T>G	p.Tyr488Asp	missense	Exon 12 of 12	ENSP00000516244.1	C9JLX5
	ZNF568	ENST00000591887.1	TSL:1	n.1631T>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26840 AN: 151810 Hom.: 2425 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.189

GnomAD2 exomes AF: 0.172 AC: 36021 AN: 209504 AF XY: 0.176

Gnomad AFR exome AF: 0.204

Gnomad AMR exome AF: 0.143

Gnomad ASJ exome AF: 0.170

Gnomad EAS exome AF: 0.172

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.164 AC: 234813 AN: 1434522 Hom.: 19834 Cov.: 59 AF XY: 0.166 AC XY: 118069 AN XY: 712058

African (AFR) AF: 0.209 AC: 6860 AN: 32772

American (AMR) AF: 0.144 AC: 5856 AN: 40598

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 4487 AN: 25748

East Asian (EAS) AF: 0.185 AC: 7090 AN: 38396

South Asian (SAS) AF: 0.241 AC: 20082 AN: 83432

European-Finnish (FIN) AF: 0.165 AC: 7827 AN: 47384

Middle Eastern (MID) AF: 0.221 AC: 1268 AN: 5750

European-Non Finnish (NFE) AF: 0.156 AC: 171305 AN: 1100774

Other (OTH) AF: 0.168 AC: 10038 AN: 59668

GnomAD4 genome AF: 0.177 AC: 26865 AN: 151928 Hom.: 2431 Cov.: 32 AF XY: 0.178 AC XY: 13232 AN XY: 74260

African (AFR) AF: 0.206 AC: 8537 AN: 41426

American (AMR) AF: 0.171 AC: 2607 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 620 AN: 3470

East Asian (EAS) AF: 0.169 AC: 869 AN: 5146

South Asian (SAS) AF: 0.261 AC: 1253 AN: 4796

European-Finnish (FIN) AF: 0.172 AC: 1820 AN: 10558

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10559 AN: 67954

Other (OTH) AF: 0.188 AC: 396 AN: 2106

Alfa AF: 0.159 Hom.: 3659

Bravo AF: 0.175

TwinsUK AF: 0.166 AC: 614

ALSPAC AF: 0.168 AC: 647

ExAC AF: 0.159 AC: 19087

Asia WGS AF: 0.221 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-1.1	T
PhyloP100		7.6
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.46
ClinPred		0.048	T
GERP RS		3.9
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10405238; hg19: chr19-37488055; COSMIC: COSV71278484; COSMIC: COSV71278484;