10-43557002-A-C

Variant names:

• chr10-43557002-A-C
• NM_001099282.2:c.1078T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001099282.2(ZNF239):​c.1078T>G​(p.Ser360Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ZNF239 NM_001099282.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.349

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26776338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF239	NM_001099282.2	c.1078T>G	p.Ser360Ala	missense_variant	Exon 4 of 4	ENST00000374446.7	NP_001092752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF239	ENST00000374446.7	c.1078T>G	p.Ser360Ala	missense_variant	Exon 4 of 4	1	NM_001099282.2	ENSP00000363569.1
ZNF239	ENST00000306006.10	c.1078T>G	p.Ser360Ala	missense_variant	Exon 2 of 2	1		ENSP00000307774.6
ZNF239	ENST00000426961.1	c.1078T>G	p.Ser360Ala	missense_variant	Exon 3 of 3	2		ENSP00000398202.1
ZNF239	ENST00000535642.5	c.1078T>G	p.Ser360Ala	missense_variant	Exon 2 of 2	2		ENSP00000443907.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461874 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727240

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: 0.00000450

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1078T>G (p.S360A) alteration is located in exon 2 (coding exon 1) of the ZNF239 gene. This alteration results from a T to G substitution at nucleotide position 1078, causing the serine (S) at amino acid position 360 to be replaced by an alanine (A). 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	Benign	0.32
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T;T;T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.48	.;.;.;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;L;L
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Benign	0.10
Sift	Benign	0.032	D;D;D;D
Sift4G	Benign	0.073	T;T;T;T
Polyphen		0.99	D;D;D;D
Vest4		0.33
MutPred		0.67		Loss of disorder (P = 0.0224);Loss of disorder (P = 0.0224);Loss of disorder (P = 0.0224);Loss of disorder (P = 0.0224);
MVP		0.29
MPC		0.30
ClinPred		0.93	D
GERP RS		3.6
Varity_R		0.19
gMVP		0.0086

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: chr10-44052450;