rs935706

Variant names:

• chr19-36996730-G-A
• rs935706
• ENST00000444991.6:c.1039G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-36996730-G-A
• chr19-36996730-G-C

Variant summary

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

The ENST00000444991.6(ZNF568):​c.1039G>A​(p.Ala347Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,536,624 control chromosomes in the GnomAD database, including 214,964 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 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 0.54 (22285 hom., cov: 32)
  • Exomes 𝑓: 0.53 (192679 hom.)
• Consequence: ZNF568 ENST00000444991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498
• Publications: 20 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=8.822338E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.1039G>A	p.Ala347Thr	missense_variant	Exon 10 of 10		NP_001191767.1
ZNF568	NM_001204839.2	c.847G>A	p.Ala283Thr	missense_variant	Exon 9 of 9		NP_001191768.1
ZNF568	XM_017026772.2	c.1039G>A	p.Ala347Thr	missense_variant	Exon 10 of 10		XP_016882261.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000291239	ENST00000706165.1	c.1039G>A	p.Ala347Thr	missense_variant	Exon 12 of 12			ENSP00000516244.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81250 AN: 151888 Hom.: 22251 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.538

GnomAD2 exomes AF: 0.498 AC: 70527 AN: 141688 AF XY: 0.502

Gnomad AFR exome AF: 0.611

Gnomad AMR exome AF: 0.482

Gnomad ASJ exome AF: 0.444

Gnomad EAS exome AF: 0.263

Gnomad FIN exome AF: 0.494

Gnomad NFE exome AF: 0.520

Gnomad OTH exome AF: 0.509

GnomAD4 exome AF: 0.525 AC: 726946 AN: 1384618 Hom.: 192679 Cov.: 51 AF XY: 0.525 AC XY: 358929 AN XY: 683322

African (AFR) AF: 0.613 AC: 19349 AN: 31578

American (AMR) AF: 0.492 AC: 17522 AN: 35646

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 11280 AN: 25152

East Asian (EAS) AF: 0.290 AC: 10369 AN: 35760

South Asian (SAS) AF: 0.556 AC: 44041 AN: 79162

European-Finnish (FIN) AF: 0.504 AC: 17397 AN: 34546

Middle Eastern (MID) AF: 0.550 AC: 3129 AN: 5694

European-Non Finnish (NFE) AF: 0.532 AC: 573787 AN: 1079078

Other (OTH) AF: 0.518 AC: 30072 AN: 58002

GnomAD4 genome AF: 0.535 AC: 81345 AN: 152006 Hom.: 22285 Cov.: 32 AF XY: 0.534 AC XY: 39685 AN XY: 74272

African (AFR) AF: 0.615 AC: 25521 AN: 41464

American (AMR) AF: 0.526 AC: 8039 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1554 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1375 AN: 5170

South Asian (SAS) AF: 0.560 AC: 2695 AN: 4816

European-Finnish (FIN) AF: 0.515 AC: 5429 AN: 10536

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35198 AN: 67950

Other (OTH) AF: 0.536 AC: 1134 AN: 2114

Alfa AF: 0.513 Hom.: 45121

Bravo AF: 0.536

TwinsUK AF: 0.534 AC: 1980

ALSPAC AF: 0.553 AC: 2131

ExAC AF: 0.356 AC: 32099

Asia WGS AF: 0.457 AC: 1588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.064	T;.;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.19	T;T;T;T
MetaRNN	Benign	0.0000088	T;T;T;T
MetaSVM	Benign	-0.99	T
PhyloP100		0.50
PROVEAN	Benign	-2.2	N;N;.;N
REVEL	Benign	0.028
Sift	Uncertain	0.0020	D;D;.;T
Sift4G	Uncertain	0.0020	D;D;D;D
Vest4		0.072, 0.055
ClinPred		0.0075	T
GERP RS		0.53
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: rs935706; hg19: chr19-37487632; COSMIC: COSV71278442; COSMIC: COSV71278442;