NM_001099282.2:c.1205C>T

Variant names:

• chr10-43556875-G-A
• rs200436959
• NM_001099282.2:c.1205C>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001099282.2(ZNF239):​c.1205C>T​(p.Pro402Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P402H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF239 NM_001099282.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.23
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099282.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF239	NM_001099282.2	MANE Select	c.1205C>T	p.Pro402Leu	missense	Exon 4 of 4	NP_001092752.1	Q16600
	ZNF239	NM_001324353.2		c.1544C>T	p.Pro515Leu	missense	Exon 5 of 5	NP_001311282.1
	ZNF239	NM_001324352.2		c.1331C>T	p.Pro444Leu	missense	Exon 4 of 4	NP_001311281.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF239	ENST00000374446.7	TSL:1 MANE Select	c.1205C>T	p.Pro402Leu	missense	Exon 4 of 4	ENSP00000363569.1	Q16600
	ZNF239	ENST00000306006.10	TSL:1	c.1205C>T	p.Pro402Leu	missense	Exon 2 of 2	ENSP00000307774.6	Q16600
	ZNF239	ENST00000426961.1	TSL:2	c.1205C>T	p.Pro402Leu	missense	Exon 3 of 3	ENSP00000398202.1	Q16600

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.2
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-9.7	D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.65		Loss of catalytic residue at P402 (P = 0.0285)
MVP		0.69
MPC		0.33
ClinPred		1.0	D
GERP RS		3.7
Varity_R		0.74
gMVP		0.039
Mutation Taster		=50/50

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

Other links and lift over

dbSNP: rs200436959; hg19: chr10-44052323;