11-123726637-C-T

Variant summary

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

The NM_003455.4(ZNF202):c.1307G>A(p.Arg436Gln) 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. 12/21 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: 0.291

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=0.096636534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF202	NM_003455.4	c.1307G>A	p.Arg436Gln	missense_variant	9/9	ENST00000530393.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF202	ENST00000530393.6	c.1307G>A	p.Arg436Gln	missense_variant	9/9	1	NM_003455.4	P1
ZNF202	ENST00000336139.8	c.1307G>A	p.Arg436Gln	missense_variant	8/8	1		P1
ZNF202	ENST00000529691.1	c.1307G>A	p.Arg436Gln	missense_variant	7/7	2		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

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

Jun 29, 2022

The c.1307G>A (p.R436Q) alteration is located in exon 9 (coding exon 6) of the ZNF202 gene. This alteration results from a G to A substitution at nucleotide position 1307, causing the arginine (R) at amino acid position 436 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	Pathogenic	0.89
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.066	T;T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.52	D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.097	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N;N;N
MutationTaster	Benign	0.60	D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.31	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.66	T;T;T
Sift4G	Benign	0.54	T;T;T
Polyphen		0.85	P;P;P
Vest4		0.11
MutPred		0.61		Loss of MoRF binding (P = 0.0219);Loss of MoRF binding (P = 0.0219);Loss of MoRF binding (P = 0.0219);
MVP		0.36
MPC		0.81
ClinPred		0.85	D
GERP RS		4.4
Varity_R		0.064
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr11-123597345;