20-18306324-A-G

Position:

• chr20-18306324-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001352452.2(ZNF133):​c.148A>G​(p.Ile50Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: ZNF133 NM_001352452.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06

Genes affected

ZNF133 (HGNC:12917): (zinc finger protein 133) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2061716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF133	NM_001352452.2	c.148A>G	p.Ile50Val	missense_variant	6/7	ENST00000425686.3	NP_001339381.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF133	ENST00000425686.3	c.148A>G	p.Ile50Val	missense_variant	6/7	3	NM_001352452.2	ENSP00000406638	A2
	ENST00000666293.1	n.426-16295T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2023

The c.148A>G (p.I50V) alteration is located in exon 6 (coding exon 2) of the ZNF133 gene. This alteration results from a A to G substitution at nucleotide position 148, causing the isoleucine (I) at amino acid position 50 to be replaced by a valine (V). 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
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	.;T;.;T;.;.;.;.;T;.
Eigen	Benign	-0.0092
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.41	T;.;T;T;.;T;T;T;.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.4	L;L;.;L;L;.;.;.;L;.
MutationTaster	Benign	1.0	D;D;D;N;N;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.46	.;.;.;N;N;N;.;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.081	.;.;.;T;T;D;.;T;T;T
Sift4G	Benign	0.11	T;T;T;T;T;T;T;T;T;T
Polyphen		0.54	P;B;.;B;P;.;.;.;B;.
Vest4		0.44
MutPred		0.43		Gain of ubiquitination at K46 (P = 0.1115);Gain of ubiquitination at K46 (P = 0.1115);.;Gain of ubiquitination at K46 (P = 0.1115);Gain of ubiquitination at K46 (P = 0.1115);Gain of ubiquitination at K46 (P = 0.1115);.;Gain of ubiquitination at K46 (P = 0.1115);Gain of ubiquitination at K46 (P = 0.1115);Gain of ubiquitination at K46 (P = 0.1115);
MVP		0.33
MPC		0.90
ClinPred		0.82	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.072
gMVP		0.087

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-18286968;