10-43556829-T-A

Position:

• chr10-43556829-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099282.2(ZNF239):​c.1251A>T​(p.Lys417Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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: -0.948

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14330602).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF239	NM_001099282.2	c.1251A>T	p.Lys417Asn	missense_variant	4/4	ENST00000374446.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF239	ENST00000374446.7	c.1251A>T	p.Lys417Asn	missense_variant	4/4	1	NM_001099282.2	P1
ZNF239	ENST00000306006.10	c.1251A>T	p.Lys417Asn	missense_variant	2/2	1		P1
ZNF239	ENST00000426961.1	c.1251A>T	p.Lys417Asn	missense_variant	3/3	2		P1
ZNF239	ENST00000535642.5	c.1251A>T	p.Lys417Asn	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

May 12, 2024

The c.1251A>T (p.K417N) alteration is located in exon 2 (coding exon 1) of the ZNF239 gene. This alteration results from a A to T substitution at nucleotide position 1251, causing the lysine (K) at amino acid position 417 to be replaced by an asparagine (N). 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	0.83
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.0085	T;T;T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.17	.;.;.;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N;N;N;N
MutationTaster	Benign	0.99	N;N;N;N;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	0.99	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.72	T;T;T;T
Sift4G	Benign	0.77	T;T;T;T
Polyphen		1.0	D;D;D;D
Vest4		0.063
MutPred		0.32		Loss of catalytic residue at K417 (P = 0.0109);Loss of catalytic residue at K417 (P = 0.0109);Loss of catalytic residue at K417 (P = 0.0109);Loss of catalytic residue at K417 (P = 0.0109);
MVP		0.24
MPC		0.33
ClinPred		0.38	T
GERP RS		0.17
Varity_R		0.071
gMVP		0.035

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: rs1017630178; hg19: chr10-44052277;