ENST00000444991.6:c.1039G>C

Variant names:

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

Variant summary

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

The ENST00000444991.6(ZNF568):​c.1039G>C​(p.Ala347Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 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: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ZNF568 ENST00000444991.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.498
• 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=0.11568469).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF568	NM_001204838.2	c.1039G>C	p.Ala347Pro	missense_variant	Exon 10 of 10		NP_001191767.1
ZNF568	NM_001204839.2	c.847G>C	p.Ala283Pro	missense_variant	Exon 9 of 9		NP_001191768.1
ZNF568	XM_017026772.2	c.1039G>C	p.Ala347Pro	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>C	p.Ala347Pro	missense_variant	Exon 12 of 12			ENSP00000516244.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385142 Hom.: 0 Cov.: 51 AF XY: 0.00000146 AC XY: 1 AN XY: 683560

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25184

East Asian (EAS) AF: 0.00 AC: 0 AN: 35764

South Asian (SAS) AF: 0.00 AC: 0 AN: 79212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1079412

Other (OTH) AF: 0.00 AC: 0 AN: 58020

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.074	T;.;.;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.17	T;T;T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.50
PROVEAN	Uncertain	-3.1	D;D;.;D
REVEL	Benign	0.028
Sift	Uncertain	0.022	D;D;.;D
Sift4G	Uncertain	0.0030	D;D;D;D
Vest4		0.22, 0.21
MutPred		0.47		Gain of relative solvent accessibility (P = 0.0215);.;Gain of relative solvent accessibility (P = 0.0215);.;
MVP		0.31
ClinPred		0.082	T
GERP RS		0.53
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: rs935706; hg19: chr19-37487632; COSMIC: COSV71278915; COSMIC: COSV71278915;