rs935707

Variant names:

• chr19-36996821-G-A
• rs935707
• ENST00000444991.6:c.1130G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-36996821-G-A
• chr19-36996821-G-T

Variant summary

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

The ENST00000444991.6(ZNF568):​c.1130G>A​(p.Arg377His) 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 1,550,290 control chromosomes in the GnomAD database, including 216,859 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 (22261 hom., cov: 31)
  • Exomes 𝑓: 0.52 (194598 hom.)
• Consequence: ZNF568 ENST00000444991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.94
• Publications: 19 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=8.981675E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.1130G>A	p.Arg377His	missense_variant	Exon 10 of 10		NP_001191767.1
ZNF568	NM_001204839.2	c.938G>A	p.Arg313His	missense_variant	Exon 9 of 9		NP_001191768.1
ZNF568	XM_017026772.2	c.1130G>A	p.Arg377His	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.1130G>A	p.Arg377His	missense_variant	Exon 12 of 12			ENSP00000516244.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81173 AN: 151052 Hom.: 22227 Cov.: 31

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.541

GnomAD2 exomes AF: 0.502 AC: 82628 AN: 164688 AF XY: 0.505

Gnomad AFR exome AF: 0.619

Gnomad AMR exome AF: 0.483

Gnomad ASJ exome AF: 0.443

Gnomad EAS exome AF: 0.267

Gnomad FIN exome AF: 0.511

Gnomad NFE exome AF: 0.522

Gnomad OTH exome AF: 0.510

GnomAD4 exome AF: 0.525 AC: 734457 AN: 1399114 Hom.: 194598 Cov.: 59 AF XY: 0.525 AC XY: 363254 AN XY: 691600

African (AFR) AF: 0.613 AC: 19564 AN: 31890

American (AMR) AF: 0.491 AC: 18234 AN: 37134

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 11340 AN: 25306

East Asian (EAS) AF: 0.290 AC: 10665 AN: 36784

South Asian (SAS) AF: 0.557 AC: 44491 AN: 79914

European-Finnish (FIN) AF: 0.507 AC: 18942 AN: 37392

Middle Eastern (MID) AF: 0.550 AC: 3140 AN: 5710

European-Non Finnish (NFE) AF: 0.532 AC: 577662 AN: 1086362

Other (OTH) AF: 0.519 AC: 30419 AN: 58622

GnomAD4 genome AF: 0.538 AC: 81268 AN: 151176 Hom.: 22261 Cov.: 31 AF XY: 0.537 AC XY: 39645 AN XY: 73854

African (AFR) AF: 0.617 AC: 25475 AN: 41260

American (AMR) AF: 0.528 AC: 8031 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1552 AN: 3444

East Asian (EAS) AF: 0.273 AC: 1373 AN: 5022

South Asian (SAS) AF: 0.564 AC: 2689 AN: 4768

European-Finnish (FIN) AF: 0.516 AC: 5420 AN: 10494

Middle Eastern (MID) AF: 0.561 AC: 157 AN: 280

European-Non Finnish (NFE) AF: 0.520 AC: 35195 AN: 67692

Other (OTH) AF: 0.540 AC: 1135 AN: 2102

Alfa AF: 0.512 Hom.: 37677

Bravo AF: 0.536

TwinsUK AF: 0.535 AC: 1982

ALSPAC AF: 0.553 AC: 2132

ExAC AF: 0.440 AC: 49274

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	0.10
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.046
DANN	Benign	0.87
DEOGEN2	Benign	0.0096	T;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.066	T;T;T;T
MetaRNN	Benign	0.0000090	T;T;T;T
MetaSVM	Benign	-0.94	T
PhyloP100		-4.9
PROVEAN	Benign	-0.25	N;N;.;N
REVEL	Benign	0.016
Sift	Benign	0.60	T;T;.;T
Sift4G	Benign	0.40	T;T;T;T
Vest4		0.014, 0.015
ClinPred		0.011	T
GERP RS		-3.1
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: rs935707; hg19: chr19-37487723; COSMIC: COSV71278443; COSMIC: COSV71278443;