10-43556712-A-C

Position:

• chr10-43556712-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099282.2(ZNF239):​c.1368T>G​(p.Asp456Glu) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF239 NM_001099282.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.47

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022210777).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF239	NM_001099282.2	c.1368T>G	p.Asp456Glu	missense_variant	4/4	ENST00000374446.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF239	ENST00000374446.7	c.1368T>G	p.Asp456Glu	missense_variant	4/4	1	NM_001099282.2	P1
ZNF239	ENST00000306006.10	c.1368T>G	p.Asp456Glu	missense_variant	2/2	1		P1
ZNF239	ENST00000426961.1	c.1368T>G	p.Asp456Glu	missense_variant	3/3	2		P1
ZNF239	ENST00000535642.5	c.1368T>G	p.Asp456Glu	missense_variant	2/2	2		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Apr 12, 2024

The c.1368T>G (p.D456E) 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 1368, causing the aspartic acid (D) at amino acid position 456 to be replaced by a glutamic acid (E). 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	0.15
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.14
DANN	Benign	0.72
DEOGEN2	Benign	0.0082	T;T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0070	N
LIST_S2	Benign	0.10	.;.;.;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.022	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.49	N;N;N;N
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.5	N;N;N;N
REVEL	Benign	0.024
Sift	Benign	0.30	T;T;T;T
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.058	B;B;B;B
Vest4		0.10
MutPred		0.23		Gain of methylation at K455 (P = 0.07);Gain of methylation at K455 (P = 0.07);Gain of methylation at K455 (P = 0.07);Gain of methylation at K455 (P = 0.07);
MVP		0.061
MPC		0.049
ClinPred		0.063	T
GERP RS		-6.0
Varity_R		0.051
gMVP		0.0050

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: chr10-44052160;