11-123728142-C-A

Position:

• chr11-123728142-C-A

Variant summary

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

The NM_003455.4(ZNF202):​c.823G>T​(p.Val275Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,502 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF202 NM_003455.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.109

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF202	NM_003455.4	c.823G>T	p.Val275Phe	missense_variant	7/9	ENST00000530393.6	NP_003446.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF202	ENST00000530393.6	c.823G>T	p.Val275Phe	missense_variant	7/9	1	NM_003455.4	ENSP00000432504	P1
ZNF202	ENST00000336139.8	c.823G>T	p.Val275Phe	missense_variant	6/8	1		ENSP00000337724	P1
ZNF202	ENST00000529691.1	c.823G>T	p.Val275Phe	missense_variant	5/7	2		ENSP00000433881	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457502 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 725192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

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

Jan 30, 2024

The c.823G>T (p.V275F) alteration is located in exon 7 (coding exon 4) of the ZNF202 gene. This alteration results from a G to T substitution at nucleotide position 823, causing the valine (V) at amino acid position 275 to be replaced by a phenylalanine (F). 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	0.68
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.098	T;T;T
Eigen	Benign	-0.080
Eigen_PC	Benign	-0.037
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.31	.;.;T
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	-0.045	N;N;N
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.91	N;N;N
REVEL	Benign	0.17
Sift	Benign	0.23	T;T;T
Sift4G	Uncertain	0.028	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.83
MutPred		0.40		Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);Gain of sheet (P = 0.1945);
MVP		0.67
MPC		0.87
ClinPred		0.90	D
GERP RS		4.2
Varity_R		0.090
gMVP		0.51

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: chr11-123598850;