rs7158731

Variant names:

• chr14-102326049-T-C
• rs7158731
• NM_018335.6:c.353T>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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 0.34 (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
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018335.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF839	NM_018335.6	MANE Select	c.353T>C	p.Leu118Pro	missense	Exon 2 of 8	NP_060805.3	A8K0R7-5
	ZNF839	NM_001385065.1		c.353T>C	p.Leu118Pro	missense	Exon 2 of 7	NP_001371994.1
	ZNF839	NM_001267827.2		c.5T>C	p.Leu2Pro	missense	Exon 2 of 8	NP_001254756.1	A8K0R7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF839	ENST00000442396.7	TSL:5 MANE Select	c.353T>C	p.Leu118Pro	missense	Exon 2 of 8	ENSP00000399863.2	A8K0R7-5
	ZNF839	ENST00000892181.1		c.353T>C	p.Leu118Pro	missense	Exon 2 of 7	ENSP00000562240.1
	ZNF839	ENST00000892182.1		c.353T>C	p.Leu118Pro	missense	Exon 2 of 8	ENSP00000562241.1

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

GnomAD2 exomes AF: 0.273 AC: 67482 AN: 247204 AF XY: 0.257

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 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

African (AFR) AF: 0.677 AC: 22664 AN: 33458

American (AMR) AF: 0.449 AC: 20005 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5905 AN: 26088

East Asian (EAS) AF: 0.331 AC: 13138 AN: 39656

South Asian (SAS) AF: 0.283 AC: 24378 AN: 86160

European-Finnish (FIN) AF: 0.178 AC: 9522 AN: 53374

Middle Eastern (MID) AF: 0.217 AC: 1248 AN: 5764

European-Non Finnish (NFE) AF: 0.172 AC: 191094 AN: 1111456

Other (OTH) AF: 0.227 AC: 13696 AN: 60346

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

African (AFR) AF: 0.657 AC: 27229 AN: 41472

American (AMR) AF: 0.351 AC: 5360 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 742 AN: 3472

East Asian (EAS) AF: 0.328 AC: 1694 AN: 5160

South Asian (SAS) AF: 0.295 AC: 1420 AN: 4816

European-Finnish (FIN) AF: 0.187 AC: 1980 AN: 10578

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11612 AN: 67968

Other (OTH) AF: 0.309 AC: 654 AN: 2114

Alfa AF: 0.226 Hom.: 24450

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 v4.9

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
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00079	N
LIST_S2	Benign	0.16	T
MetaRNN	Benign	0.0000083	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.6	N
PhyloP100		1.6
PrimateAI	Benign	0.29	T
PROVEAN	Benign	5.8	N
REVEL	Benign	0.065
Sift	Benign	1.0	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.098
MPC		0.14
ClinPred		0.0042	T
GERP RS		4.2
Varity_R		0.039
gMVP		0.098
Mutation Taster		=99/1	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: rs7158731; hg19: chr14-102792386; COSMIC: COSV51756154; COSMIC: COSV51756154;