10-43556977-A-G

Variant names:

• chr10-43556977-A-G
• rs748326573
• NM_001099282.2:c.1103T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099282.2(ZNF239):​c.1103T>C​(p.Ile368Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF239 NM_001099282.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0180
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101647586).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099282.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF239	NM_001099282.2	MANE Select	c.1103T>C	p.Ile368Thr	missense	Exon 4 of 4	NP_001092752.1	Q16600
	ZNF239	NM_001324353.2		c.1442T>C	p.Ile481Thr	missense	Exon 5 of 5	NP_001311282.1
	ZNF239	NM_001324352.2		c.1229T>C	p.Ile410Thr	missense	Exon 4 of 4	NP_001311281.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF239	ENST00000374446.7	TSL:1 MANE Select	c.1103T>C	p.Ile368Thr	missense	Exon 4 of 4	ENSP00000363569.1	Q16600
	ZNF239	ENST00000306006.10	TSL:1	c.1103T>C	p.Ile368Thr	missense	Exon 2 of 2	ENSP00000307774.6	Q16600
	ZNF239	ENST00000426961.1	TSL:2	c.1103T>C	p.Ile368Thr	missense	Exon 3 of 3	ENSP00000398202.1	Q16600

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461864 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727230

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.40	N
PhyloP100		0.018
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.044
Sift	Benign	0.27	T
Sift4G	Uncertain	0.058	T
Polyphen		0.085	B
Vest4		0.12
MutPred		0.62		Loss of stability (P = 0.0051)
MVP		0.055
MPC		0.057
ClinPred		0.076	T
GERP RS		-0.19
Varity_R		0.19
gMVP		0.014
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs748326573; hg19: chr10-44052425;