19-44025467-C-G

Variant names:

• chr19-44025467-C-G
• rs1165494708
• NM_001129996.2:c.31C>G

Variant summary

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

The NM_001129996.2(ZNF222):​c.31C>G​(p.Arg11Gly) 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 1,398,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R11W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ZNF222 NM_001129996.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 0 publications found

Genes affected

ZNF222 (HGNC:13015): (zinc finger protein 222) 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 regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267022 (HGNC:):

ZNF222-DT (HGNC:55310): (ZNF222 divergent transcript)

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=0.119716674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF222	NM_001129996.2	c.31C>G	p.Arg11Gly	missense_variant	Exon 1 of 4	ENST00000391960.4	NP_001123468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF222	ENST00000391960.4	c.31C>G	p.Arg11Gly	missense_variant	Exon 1 of 4	1	NM_001129996.2	ENSP00000375822.2
ENSG00000267022	ENST00000591793.1	n.31C>G		non_coding_transcript_exon_variant	Exon 1 of 11	2		ENSP00000467018.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398066 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689546

African (AFR) AF: 0.00 AC: 0 AN: 31512

American (AMR) AF: 0.00 AC: 0 AN: 35464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25052

East Asian (EAS) AF: 0.00 AC: 0 AN: 35702

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078402

Other (OTH) AF: 0.00 AC: 0 AN: 57908

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.95
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.11	T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.038
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.49	.;N
REVEL	Benign	0.017
Sift	Benign	0.056	.;T
Sift4G	Benign	0.37	T;T
Vest4		0.22
MutPred		0.32		Gain of ubiquitination at K8 (P = 0.0447);Gain of ubiquitination at K8 (P = 0.0447);
MVP		0.11
MPC		0.30
ClinPred		0.77	D
GERP RS		0.22
PromoterAI		-0.015	Neutral
gMVP		0.061
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1165494708; hg19: chr19-44529619;