10-43557455-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C209G) has been classified as Likely benign.

• 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

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 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF239	NM_001099282.2	c.625T>A	p.Cys209Ser	missense_variant	4/4	ENST00000374446.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF239	ENST00000374446.7	c.625T>A	p.Cys209Ser	missense_variant	4/4	1	NM_001099282.2	P1
ZNF239	ENST00000306006.10	c.625T>A	p.Cys209Ser	missense_variant	2/2	1		P1
ZNF239	ENST00000426961.1	c.625T>A	p.Cys209Ser	missense_variant	3/3	2		P1
ZNF239	ENST00000535642.5	c.625T>A	p.Cys209Ser	missense_variant	2/2	2		P1

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

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;T
Eigen	Uncertain	0.38
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.79	D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.88	D;D;D;D
MetaSVM	Uncertain	0.41	D
MutationAssessor	Pathogenic	3.3	M;M;M;M
MutationTaster	Benign	0.26	P;P;P;P;P
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-9.1	D;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.71
MutPred		0.50		Gain of ubiquitination at K205 (P = 0.0453);Gain of ubiquitination at K205 (P = 0.0453);Gain of ubiquitination at K205 (P = 0.0453);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

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

LitVar

Other links and lift over

dbSNP: rs2230661; hg19: chr10-44052903;