10-43557455-A-T

Variant names:

• chr10-43557455-A-T
• rs2230661
• NM_001099282.2:c.625T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001099282.2(ZNF239):​c.625T>A​(p.Cys209Ser) 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF239 NM_001099282.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.57
• Publications: 41 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF239	NM_001099282.2	MANE Select	c.625T>A	p.Cys209Ser	missense	Exon 4 of 4	NP_001092752.1
	ZNF239	NM_001324353.2		c.964T>A	p.Cys322Ser	missense	Exon 5 of 5	NP_001311282.1
	ZNF239	NM_001324352.2		c.751T>A	p.Cys251Ser	missense	Exon 4 of 4	NP_001311281.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF239	ENST00000374446.7	TSL:1 MANE Select	c.625T>A	p.Cys209Ser	missense	Exon 4 of 4	ENSP00000363569.1
	ZNF239	ENST00000306006.10	TSL:1	c.625T>A	p.Cys209Ser	missense	Exon 2 of 2	ENSP00000307774.6
	ZNF239	ENST00000426961.1	TSL:2	c.625T>A	p.Cys209Ser	missense	Exon 3 of 3	ENSP00000398202.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461848 Hom.: 0 Cov.: 67 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.38
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-9.1	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.50		Gain of ubiquitination at K205 (P = 0.0453)
MVP		0.74
MPC		0.33
ClinPred		1.0	D
GERP RS		2.9
Varity_R		0.54
gMVP		0.15
Mutation Taster		=95/5	polymorphism

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: rs2230661; hg19: chr10-44052903;