10-43556875-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001099282.2(ZNF239):c.1205C>A(p.Pro402His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF239 NM_001099282.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.23

Genes affected

ZNF239 (HGNC:13031): (zinc finger protein 239) MOK2 proteins are DNA- and RNA-binding proteins that are mainly associated with nuclear RNP components, including the nucleoli and extranucleolar structures (Arranz et al., 1997 [PubMed 9121460]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF239	NM_001099282.2	c.1205C>A	p.Pro402His	missense_variant	4/4	ENST00000374446.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF239	ENST00000374446.7	c.1205C>A	p.Pro402His	missense_variant	4/4	1	NM_001099282.2	P1
ZNF239	ENST00000306006.10	c.1205C>A	p.Pro402His	missense_variant	2/2	1		P1
ZNF239	ENST00000426961.1	c.1205C>A	p.Pro402His	missense_variant	3/3	2		P1
ZNF239	ENST00000535642.5	c.1205C>A	p.Pro402His	missense_variant	2/2	2		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 17, 2023

The c.1205C>A (p.P402H) alteration is located in exon 2 (coding exon 1) of the ZNF239 gene. This alteration results from a C to A substitution at nucleotide position 1205, causing the proline (P) at amino acid position 402 to be replaced by a histidine (H). 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	0.99
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;T;T
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.77	D
M_CAP	Benign	0.0079	T
MetaRNN	Pathogenic	0.80	D;D;D;D
MetaSVM	Uncertain	0.0018	D
MutationAssessor	Pathogenic	3.0	M;M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-8.7	D;D;D;D
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.70
MutPred		0.64		Gain of MoRF binding (P = 0.1264);Gain of MoRF binding (P = 0.1264);Gain of MoRF binding (P = 0.1264);Gain of MoRF binding (P = 0.1264);
MVP		0.67
MPC		0.34
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.76
gMVP		0.043

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: chr10-44052323; COSMIC: COSV60019032; COSMIC: COSV60019032;