10-43557565-G-C

Variant names:

• chr10-43557565-G-C
• rs2230660
• NM_001099282.2:c.515C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099282.2(ZNF239):​c.515C>G​(p.Ala172Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 1,613,678 control chromosomes in the GnomAD database, including 236,324 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (22130 hom., cov: 33)
  • Exomes 𝑓: 0.54 (214194 hom.)
• Consequence: ZNF239 NM_001099282.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531
• Publications: 37 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.95043E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF239	NM_001099282.2	MANE Select	c.515C>G	p.Ala172Gly	missense	Exon 4 of 4	NP_001092752.1
	ZNF239	NM_001324353.2		c.854C>G	p.Ala285Gly	missense	Exon 5 of 5	NP_001311282.1
	ZNF239	NM_001324352.2		c.641C>G	p.Ala214Gly	missense	Exon 4 of 4	NP_001311281.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF239	ENST00000374446.7	TSL:1 MANE Select	c.515C>G	p.Ala172Gly	missense	Exon 4 of 4	ENSP00000363569.1
	ZNF239	ENST00000306006.10	TSL:1	c.515C>G	p.Ala172Gly	missense	Exon 2 of 2	ENSP00000307774.6
	ZNF239	ENST00000426961.1	TSL:2	c.515C>G	p.Ala172Gly	missense	Exon 3 of 3	ENSP00000398202.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81449 AN: 151964 Hom.: 22111 Cov.: 33

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.539

GnomAD2 exomes AF: 0.552 AC: 137600 AN: 249110 AF XY: 0.557

Gnomad AFR exome AF: 0.515

Gnomad AMR exome AF: 0.506

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.549

Gnomad FIN exome AF: 0.623

Gnomad NFE exome AF: 0.551

Gnomad OTH exome AF: 0.548

GnomAD4 exome AF: 0.540 AC: 789678 AN: 1461598 Hom.: 214194 Cov.: 65 AF XY: 0.542 AC XY: 394408 AN XY: 727118

African (AFR) AF: 0.516 AC: 17260 AN: 33474

American (AMR) AF: 0.506 AC: 22632 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 12502 AN: 26134

East Asian (EAS) AF: 0.553 AC: 21946 AN: 39700

South Asian (SAS) AF: 0.609 AC: 52504 AN: 86256

European-Finnish (FIN) AF: 0.623 AC: 33232 AN: 53304

Middle Eastern (MID) AF: 0.590 AC: 3406 AN: 5768

European-Non Finnish (NFE) AF: 0.534 AC: 593650 AN: 1111854

Other (OTH) AF: 0.539 AC: 32546 AN: 60390

GnomAD4 genome AF: 0.536 AC: 81519 AN: 152080 Hom.: 22130 Cov.: 33 AF XY: 0.541 AC XY: 40181 AN XY: 74334

African (AFR) AF: 0.510 AC: 21132 AN: 41474

American (AMR) AF: 0.508 AC: 7760 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1632 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2841 AN: 5176

South Asian (SAS) AF: 0.605 AC: 2908 AN: 4804

European-Finnish (FIN) AF: 0.628 AC: 6645 AN: 10578

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36765 AN: 67970

Other (OTH) AF: 0.544 AC: 1151 AN: 2116

Alfa AF: 0.526 Hom.: 14955

Bravo AF: 0.527

TwinsUK AF: 0.535 AC: 1983

ALSPAC AF: 0.544 AC: 2095

ESP6500AA AF: 0.528 AC: 2065

ESP6500EA AF: 0.536 AC: 4459

ExAC AF: 0.557 AC: 67289

Asia WGS AF: 0.604 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.3
DANN	Uncertain	0.97
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.00030	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.53
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.036
Sift	Benign	0.046	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.50	P
Vest4		0.12
MPC		0.068
ClinPred		0.0074	T
GERP RS		0.27
Varity_R		0.071
gMVP		0.013
Mutation Taster		=100/0	polymorphism (auto)

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: rs2230660; hg19: chr10-44053013; COSMIC: COSV60018577;