rs7158731

Positions:

• chr14-102326049-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018335.6(ZNF839):​c.353T>C​(p.Leu118Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,612,896 control chromosomes in the GnomAD database, including 50,103 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (11877 hom., cov: 31)
  • Exomes 𝑓: 0.21 (38226 hom.)
• Consequence: ZNF839 NM_018335.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

Genes affected

ZNF839 (HGNC:20345): (zinc finger protein 839) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.316703E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF839	NM_018335.6	c.353T>C	p.Leu118Pro	missense_variant	2/8	ENST00000442396.7	NP_060805.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF839	ENST00000442396.7	c.353T>C	p.Leu118Pro	missense_variant	2/8	5	NM_018335.6	ENSP00000399863	A2
ZNF839	ENST00000558850.5	c.5T>C	p.Leu2Pro	missense_variant	2/8	2		ENSP00000453363	P2
ZNF839	ENST00000559185.5	c.5T>C	p.Leu2Pro	missense_variant	2/8	2		ENSP00000453109	P2
ZNF839	ENST00000559098.5	c.161T>C	p.Leu54Pro	missense_variant, NMD_transcript_variant	2/9	2		ENSP00000453515

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50861 AN: 151960 Hom.: 11840 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.305

GnomAD3 exomes AF: 0.273 AC: 67482 AN: 247204 Hom.: 11970 AF XY: 0.257 AC XY: 34543 AN XY: 134190

Gnomad AFR exome AF: 0.662

Gnomad AMR exome AF: 0.459

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.340

Gnomad SAS exome AF: 0.282

Gnomad FIN exome AF: 0.176

Gnomad NFE exome AF: 0.175

Gnomad OTH exome AF: 0.230

GnomAD4 exome AF: 0.206 AC: 301650 AN: 1460818 Hom.: 38226 Cov.: 33 AF XY: 0.206 AC XY: 149820 AN XY: 726662

Gnomad4 AFR exome AF: 0.677

Gnomad4 AMR exome AF: 0.449

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.331

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.335 AC: 50964 AN: 152078 Hom.: 11877 Cov.: 31 AF XY: 0.334 AC XY: 24814 AN XY: 74346

Gnomad4 AFR AF: 0.657

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.309

Alfa AF: 0.204 Hom.: 9372

Bravo AF: 0.366

TwinsUK AF: 0.181 AC: 673

ALSPAC AF: 0.171 AC: 659

ESP6500AA AF: 0.625 AC: 2401

ESP6500EA AF: 0.171 AC: 1417

ExAC AF: 0.273 AC: 32990

Asia WGS AF: 0.342 AC: 1189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.031
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.0
DANN	Benign	0.68
DEOGEN2	Benign	0.0011	T;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00079	N
LIST_S2	Benign	0.16	.;T;T
MetaRNN	Benign	0.0000083	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.6	N;N;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	5.8	N;N;N
REVEL	Benign	0.065
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.098
MPC		0.14
ClinPred		0.0042	T
GERP RS		4.2
Varity_R		0.039
gMVP		0.098

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: rs7158731; hg19: chr14-102792386; COSMIC: COSV51756154; COSMIC: COSV51756154;