10-43557151-T-A

Variant summary

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

The NM_001099282.2(ZNF239):c.929A>T(p.Gln310Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,712 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF239 NM_001099282.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07

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=0.30009615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF239	NM_001099282.2	c.929A>T	p.Gln310Leu	missense_variant	4/4	ENST00000374446.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF239	ENST00000374446.7	c.929A>T	p.Gln310Leu	missense_variant	4/4	1	NM_001099282.2	P1
ZNF239	ENST00000306006.10	c.929A>T	p.Gln310Leu	missense_variant	2/2	1		P1
ZNF239	ENST00000426961.1	c.929A>T	p.Gln310Leu	missense_variant	3/3	2		P1
ZNF239	ENST00000535642.5	c.929A>T	p.Gln310Leu	missense_variant	2/2	2		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461712 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727170

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

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

Oct 03, 2022

The c.929A>T (p.Q310L) 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 929, causing the glutamine (Q) at amino acid position 310 to be replaced by a leucine (L). 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	0.29
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T;T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.31	N
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.57	N;N;N;N
MutationTaster	Benign	0.94	N;N;N;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.6	D;D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.011	D;D;D;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.95	P;P;P;P
Vest4		0.48
MutPred		0.41		Loss of disorder (P = 0.0289);Loss of disorder (P = 0.0289);Loss of disorder (P = 0.0289);Loss of disorder (P = 0.0289);
MVP		0.33
MPC		0.11
ClinPred		0.76	D
GERP RS		3.8
Varity_R		0.39
gMVP		0.14

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: rs1179676921; hg19: chr10-44052599;