rs1667354

Variant names:

• chr19-36991249-A-G
• rs1667354
• ENST00000444991.6:c.479A>G

Variant summary

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

The ENST00000444991.6(ZNF568):​c.479A>G​(p.Asp160Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 1,534,716 control chromosomes in the GnomAD database, including 225,748 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (24509 hom., cov: 32)
  • Exomes 𝑓: 0.54 (201239 hom.)
• Consequence: ZNF568 ENST00000444991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 24 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=8.637041E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.479A>G	p.Asp160Gly	missense_variant	Exon 8 of 10		NP_001191767.1
ZNF568	NM_001204839.2	c.287A>G	p.Asp96Gly	missense_variant	Exon 7 of 9		NP_001191768.1
ZNF568	XM_017026772.2	c.479A>G	p.Asp160Gly	missense_variant	Exon 8 of 10		XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000291239	ENST00000706165.1	c.479A>G	p.Asp160Gly	missense_variant	Exon 10 of 12			ENSP00000516244.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84876 AN: 151902 Hom.: 24471 Cov.: 32

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.552

GnomAD2 exomes AF: 0.510 AC: 70413 AN: 138030 AF XY: 0.514

Gnomad AFR exome AF: 0.673

Gnomad AMR exome AF: 0.487

Gnomad ASJ exome AF: 0.457

Gnomad EAS exome AF: 0.262

Gnomad FIN exome AF: 0.523

Gnomad NFE exome AF: 0.530

Gnomad OTH exome AF: 0.520

GnomAD4 exome AF: 0.537 AC: 741934 AN: 1382696 Hom.: 201239 Cov.: 40 AF XY: 0.537 AC XY: 366201 AN XY: 682232

African (AFR) AF: 0.676 AC: 21345 AN: 31558

American (AMR) AF: 0.498 AC: 17687 AN: 35492

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 11627 AN: 25140

East Asian (EAS) AF: 0.289 AC: 10318 AN: 35706

South Asian (SAS) AF: 0.567 AC: 44799 AN: 78976

European-Finnish (FIN) AF: 0.530 AC: 18022 AN: 34028

Middle Eastern (MID) AF: 0.559 AC: 3186 AN: 5696

European-Non Finnish (NFE) AF: 0.542 AC: 584111 AN: 1078168

Other (OTH) AF: 0.532 AC: 30839 AN: 57932

GnomAD4 genome AF: 0.559 AC: 84975 AN: 152020 Hom.: 24509 Cov.: 32 AF XY: 0.558 AC XY: 41464 AN XY: 74310

African (AFR) AF: 0.673 AC: 27899 AN: 41454

American (AMR) AF: 0.536 AC: 8186 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.461 AC: 1598 AN: 3468

East Asian (EAS) AF: 0.264 AC: 1361 AN: 5164

South Asian (SAS) AF: 0.571 AC: 2744 AN: 4808

European-Finnish (FIN) AF: 0.546 AC: 5765 AN: 10550

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.527 AC: 35860 AN: 67982

Other (OTH) AF: 0.550 AC: 1159 AN: 2106

Alfa AF: 0.524 Hom.: 70805

Bravo AF: 0.560

TwinsUK AF: 0.543 AC: 2012

ALSPAC AF: 0.562 AC: 2166

ExAC AF: 0.494 AC: 9608

Asia WGS AF: 0.468 AC: 1629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T;.;.;.
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.18	T;T;T;T
MetaRNN	Benign	0.0000086	T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.32
PROVEAN	Benign	-2.2	N;N;.;D
REVEL	Benign	0.051
Sift	Benign	0.20	T;T;.;D
Sift4G	Benign	0.15	T;T;T;D
Vest4		0.10, 0.048
ClinPred		0.0037	T
GERP RS		2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1667354; hg19: chr19-37482151; COSMIC: COSV71278669; COSMIC: COSV71278669;