Genetic Variant NM_001129996.2:c.31C>T (chr19-44025467-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001129996.2(ZNF222):c.31C>T(p.Arg11Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF222
NM_001129996.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0380

Publications

0 publications found

Variant links:

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]

ZNF222 links:

ENSG00000267022 (HGNC:):

ENSG00000267022 links:

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

ZNF222-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.14509311).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF222	NM_001129996.2 link	c.31C>T	p.Arg11Trp	missense_variant	Exon 1 of 4	ENST00000391960.4	NP_001123468.1	Q9UK12-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF222	ENST00000391960.4 link	c.31C>T	p.Arg11Trp	missense_variant	Exon 1 of 4	1	NM_001129996.2	ENSP00000375822.2		Q9UK12-2
ENSG00000267022	ENST00000591793.1 link	n.31C>T		non_coding_transcript_exon_variant	Exon 1 of 11	2		ENSP00000467018.1		K7ENM7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1398066

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689546

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31512

American (AMR)

AF:

0.00

AC:

AN:

35464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25052

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35702

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078402

Other (OTH)

AF:

0.00

AC:

AN:

57908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.31C>T (p.R11W) alteration is located in exon 1 (coding exon 1) of the ZNF222 gene. This alteration results from a C to T substitution at nucleotide position 31, causing the arginine (R) at amino acid position 11 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.20

T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

PhyloP100

-0.038

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.048

Sift

Uncertain

0.010

.;D

Sift4G

Uncertain

0.017

D;D

Vest4

0.21

MutPred

0.37

Loss of disorder (P = 0.0069);Loss of disorder (P = 0.0069);

MVP

0.19

MPC

0.31

ClinPred

0.83

GERP RS

0.22

PromoterAI

-0.043

Neutral

(source)

gMVP

0.060

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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NM_001129996.2:c.31C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over