rs2230661

Variant names:

• chr10-43557455-A-C
• rs2230661
• NM_001099282.2:c.625T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-43557455-A-C
• chr10-43557455-A-G
• chr10-43557455-A-T

Variant summary

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

The NM_001099282.2(ZNF239):​c.625T>G​(p.Cys209Gly) variant causes a missense change. The variant allele was found at a frequency of 0.54 in 1,613,868 control chromosomes in the GnomAD database, including 236,367 homozygotes. In-silico tool predicts 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 (22125 hom., cov: 33)
  • Exomes 𝑓: 0.54 (214242 hom.)
• Consequence: ZNF239 NM_001099282.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.57
• Publications: 41 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=1.8540025E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF239	NM_001099282.2	c.625T>G	p.Cys209Gly	missense_variant	Exon 4 of 4	ENST00000374446.7	NP_001092752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF239	ENST00000374446.7	c.625T>G	p.Cys209Gly	missense_variant	Exon 4 of 4	1	NM_001099282.2	ENSP00000363569.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81449 AN: 151984 Hom.: 22106 Cov.: 33

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.552

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: 137828 AN: 249516 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: 789849 AN: 1461766 Hom.: 214242 Cov.: 67 AF XY: 0.542 AC XY: 394496 AN XY: 727194

African (AFR) AF: 0.516 AC: 17266 AN: 33478

American (AMR) AF: 0.506 AC: 22628 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 12503 AN: 26136

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

South Asian (SAS) AF: 0.609 AC: 52511 AN: 86256

European-Finnish (FIN) AF: 0.623 AC: 33266 AN: 53382

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

European-Non Finnish (NFE) AF: 0.534 AC: 593771 AN: 1111940

Other (OTH) AF: 0.539 AC: 32552 AN: 60392

GnomAD4 genome AF: 0.536 AC: 81520 AN: 152102 Hom.: 22125 Cov.: 33 AF XY: 0.541 AC XY: 40200 AN XY: 74374

African (AFR) AF: 0.509 AC: 21129 AN: 41478

American (AMR) AF: 0.508 AC: 7761 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3468

East Asian (EAS) AF: 0.551 AC: 2844 AN: 5166

South Asian (SAS) AF: 0.605 AC: 2922 AN: 4826

European-Finnish (FIN) AF: 0.628 AC: 6650 AN: 10594

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

European-Non Finnish (NFE) AF: 0.541 AC: 36752 AN: 67964

Other (OTH) AF: 0.544 AC: 1149 AN: 2114

Alfa AF: 0.536 Hom.: 79416

Bravo AF: 0.528

TwinsUK AF: 0.534 AC: 1981

ALSPAC AF: 0.544 AC: 2096

ESP6500AA AF: 0.533 AC: 2162

ESP6500EA AF: 0.535 AC: 4483

ExAC AF: 0.557 AC: 67337

Asia WGS AF: 0.604 AC: 2100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Uncertain	0.52	D;D;D;D
Eigen	Uncertain	0.39
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.083	.;.;.;T
MetaRNN	Benign	0.00019	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Pathogenic	3.7	H;H;H;H
PhyloP100		4.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-11	D;D;D;D
REVEL	Uncertain	0.29
Sift	Uncertain	0.0080	D;D;D;D
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.48
MPC		0.34
ClinPred		0.13	T
GERP RS		2.9
Varity_R		0.42
gMVP		0.19
Mutation Taster		=97/3	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: rs2230661; hg19: chr10-44052903; COSMIC: COSV60018763; COSMIC: COSV60018763;