10-43558137-C-T

Variant names:

• chr10-43558137-C-T
• rs2999278
• NM_001099282.2:c.-58G>A

Variant summary

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

The NM_001099282.2(ZNF239):​c.-58G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 1,524,316 control chromosomes in the GnomAD database, including 222,535 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 (22110 hom., cov: 32)
  • Exomes 𝑓: 0.54 (200425 hom.)
• Consequence: ZNF239 NM_001099282.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.324
• Publications: 8 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 (BayesDel_noAF=-0.73).
• 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.-58G>A		5_prime_UTR_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.-58G>A		5_prime_UTR_variant	Exon 4 of 4	1	NM_001099282.2	ENSP00000363569.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81412 AN: 151910 Hom.: 22091 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.471

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

GnomAD4 exome AF: 0.540 AC: 740616 AN: 1372288 Hom.: 200425 Cov.: 40 AF XY: 0.541 AC XY: 364959 AN XY: 674126

African (AFR) AF: 0.516 AC: 15720 AN: 30488

American (AMR) AF: 0.505 AC: 15443 AN: 30584

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 10240 AN: 21452

East Asian (EAS) AF: 0.553 AC: 20767 AN: 37536

South Asian (SAS) AF: 0.610 AC: 44699 AN: 73236

European-Finnish (FIN) AF: 0.624 AC: 30922 AN: 49534

Middle Eastern (MID) AF: 0.588 AC: 3187 AN: 5420

European-Non Finnish (NFE) AF: 0.533 AC: 569248 AN: 1067524

Other (OTH) AF: 0.538 AC: 30390 AN: 56514

GnomAD4 genome AF: 0.536 AC: 81483 AN: 152028 Hom.: 22110 Cov.: 32 AF XY: 0.541 AC XY: 40164 AN XY: 74294

African (AFR) AF: 0.510 AC: 21140 AN: 41460

American (AMR) AF: 0.507 AC: 7743 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1633 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2835 AN: 5166

South Asian (SAS) AF: 0.606 AC: 2913 AN: 4810

European-Finnish (FIN) AF: 0.628 AC: 6631 AN: 10558

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

European-Non Finnish (NFE) AF: 0.541 AC: 36757 AN: 67984

Other (OTH) AF: 0.544 AC: 1147 AN: 2110

Alfa AF: 0.535 Hom.: 12181

Bravo AF: 0.527

Asia WGS AF: 0.604 AC: 2101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.3
DANN	Benign	0.73
PhyloP100		-0.32
Mutation Taster		=300/0	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: rs2999278; hg19: chr10-44053585; COSMIC: COSV60018588;