11-123726869-C-G

Position:

• chr11-123726869-C-G

Variant summary

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

The NM_003455.4(ZNF202):​c.1075G>C​(p.Glu359Gln) 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: 33)
• Consequence: ZNF202 NM_003455.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.674

Genes affected

ZNF202 (HGNC:12994): (zinc finger protein 202) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in chromosome; nuclear body; and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.12868497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF202	NM_003455.4	c.1075G>C	p.Glu359Gln	missense_variant	9/9	ENST00000530393.6	NP_003446.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF202	ENST00000530393.6	c.1075G>C	p.Glu359Gln	missense_variant	9/9	1	NM_003455.4	ENSP00000432504	P1
ZNF202	ENST00000336139.8	c.1075G>C	p.Glu359Gln	missense_variant	8/8	1		ENSP00000337724	P1
ZNF202	ENST00000529691.1	c.1075G>C	p.Glu359Gln	missense_variant	7/7	2		ENSP00000433881	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

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

Dec 17, 2021

The c.1075G>C (p.E359Q) alteration is located in exon 9 (coding exon 6) of the ZNF202 gene. This alteration results from a G to C substitution at nucleotide position 1075, causing the glutamic acid (E) at amino acid position 359 to be replaced by a glutamine (Q). 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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.80	.;.;T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.0	M;M;M
MutationTaster	Benign	0.92	D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.72	N;N;N
REVEL	Benign	0.068
Sift	Benign	0.056	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.15	B;B;B
Vest4		0.27
MutPred		0.32		Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);
MVP		0.45
MPC		0.54
ClinPred		0.26	T
GERP RS		4.4
Varity_R		0.094
gMVP		0.18

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

LitVar

Other links and lift over

dbSNP: rs1861170526; hg19: chr11-123597577;