10-43557565-G-C

Position:

• chr10-43557565-G-C

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF239	NM_001099282.2	c.515C>G	p.Ala172Gly	missense_variant	4/4	ENST00000374446.7	NP_001092752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF239	ENST00000374446.7	c.515C>G	p.Ala172Gly	missense_variant	4/4	1	NM_001099282.2	ENSP00000363569	P1

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

GnomAD3 exomes AF: 0.552 AC: 137600 AN: 249110 Hom.: 38207 AF XY: 0.557 AC XY: 75240 AN XY: 135162

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 SAS exome AF: 0.607

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

Gnomad4 AFR exome AF: 0.516

Gnomad4 AMR exome AF: 0.506

Gnomad4 ASJ exome AF: 0.478

Gnomad4 EAS exome AF: 0.553

Gnomad4 SAS exome AF: 0.609

Gnomad4 FIN exome AF: 0.623

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.539

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

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.628

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.544

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 v4.3

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;T;T;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;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L;L;L;L
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Benign	0.036
Sift	Benign	0.046	D;D;D;D
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.50	P;P;P;P
Vest4		0.12
MPC		0.068
ClinPred		0.0074	T
GERP RS		0.27
Varity_R		0.071
gMVP		0.013

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