19-36996821-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000444991.6(ZNF568):​c.1130G>T​(p.Arg377Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 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: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZNF568 ENST00000444991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.94
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07950586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.1130G>T	p.Arg377Leu	missense_variant	Exon 10 of 10		NP_001191767.1
ZNF568	NM_001204839.2	c.938G>T	p.Arg313Leu	missense_variant	Exon 9 of 9		NP_001191768.1
ZNF568	XM_017026772.2	c.1130G>T	p.Arg377Leu	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>T	p.Arg377Leu	missense_variant	Exon 12 of 12			ENSP00000516244.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399570 Hom.: 0 Cov.: 59 AF XY: 0.00 AC XY: 0 AN XY: 691830

African (AFR) AF: 0.00 AC: 0 AN: 31900

American (AMR) AF: 0.00 AC: 0 AN: 37172

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25328

East Asian (EAS) AF: 0.00 AC: 0 AN: 36790

South Asian (SAS) AF: 0.00 AC: 0 AN: 79950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 9.20e-7 AC: 1 AN: 1086670

Other (OTH) AF: 0.00 AC: 0 AN: 58636

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.072
DANN	Benign	0.97
DEOGEN2	Benign	0.0062	T;.;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.033	T;T;T;T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.080	T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-4.9
PROVEAN	Uncertain	-2.8	D;D;.;N
REVEL	Benign	0.013
Sift	Benign	0.55	T;T;.;T
Sift4G	Benign	0.26	T;T;T;T
Vest4		0.14, 0.16
MutPred		0.45		Loss of MoRF binding (P = 0.0027);.;Loss of MoRF binding (P = 0.0027);.;
MVP		0.12
ClinPred		0.098	T
GERP RS		-3.1
Mutation Taster		=100/0	polymorphism

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;