chr20-18315501-G-A

Position:

• chr20-18315501-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001352452.2(ZNF133):​c.650G>A​(p.Gly217Glu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF133 NM_001352452.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.347

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05649194).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF133	NM_001352452.2	c.650G>A	p.Gly217Glu	missense_variant	7/7	ENST00000425686.3	NP_001339381.2
ZNF133-AS1	XR_937299.4	n.574-1538C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF133	ENST00000425686.3	c.650G>A	p.Gly217Glu	missense_variant	7/7	3	NM_001352452.2	ENSP00000406638	A2
	ENST00000666293.1	n.425+8143C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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

Mar 18, 2024

The c.647G>A (p.G216E) alteration is located in exon 7 (coding exon 3) of the ZNF133 gene. This alteration results from a G to A substitution at nucleotide position 647, causing the glycine (G) at amino acid position 216 to be replaced by a glutamic acid (E). 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	0.095
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.72
DEOGEN2	Benign	0.016	.;.;T;.;.;T;.;.;.;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.15	T;T;.;T;T;T;.;T;T;.
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.056	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	.;.;L;.;.;L;.;.;.;L
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.4	.;.;.;.;N;N;N;.;.;N
REVEL	Benign	0.040
Sift	Benign	0.33	.;.;.;.;T;T;T;.;.;T
Sift4G	Benign	0.78	T;T;T;T;T;T;T;T;T;T
Polyphen		0.0020, 0.0010	.;B;B;.;.;B;B;.;.;B
Vest4		0.20
MutPred		0.24		.;.;Gain of solvent accessibility (P = 0.1456);.;.;Gain of solvent accessibility (P = 0.1456);.;.;.;Gain of solvent accessibility (P = 0.1456);
MVP		0.31
MPC		0.50
ClinPred		0.14	T
GERP RS		0.92
Varity_R		0.039
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr20-18296145;