11-123726171-C-A

Position:

• chr11-123726171-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003455.4(ZNF202):​c.1773G>T​(p.Arg591Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF202 NM_003455.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.496

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34705886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF202	NM_003455.4	c.1773G>T	p.Arg591Ser	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.1773G>T	p.Arg591Ser	missense_variant	9/9	1	NM_003455.4	ENSP00000432504	P1
ZNF202	ENST00000336139.8	c.1773G>T	p.Arg591Ser	missense_variant	8/8	1		ENSP00000337724	P1
ZNF202	ENST00000529691.1	c.1773G>T	p.Arg591Ser	missense_variant	7/7	2		ENSP00000433881	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Aug 08, 2022

The c.1773G>T (p.R591S) alteration is located in exon 9 (coding exon 6) of the ZNF202 gene. This alteration results from a G to T substitution at nucleotide position 1773, causing the arginine (R) at amino acid position 591 to be replaced by a serine (S). 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	0.81
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;T;T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.50	.;.;T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.1	M;M;M
MutationTaster	Benign	0.55	N;N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		0.99	D;D;D
Vest4		0.30
MutPred		0.49		Loss of catalytic residue at R591 (P = 0.0179);Loss of catalytic residue at R591 (P = 0.0179);Loss of catalytic residue at R591 (P = 0.0179);
MVP		0.58
MPC		0.27
ClinPred		0.85	D
GERP RS		3.2
Varity_R		0.29
gMVP		0.35

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: chr11-123596879;