dbSNP rs7158731: ZNF839:p.Leu118Pro (chr14-102326049-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.57

Publications

25 publications found

Variant links:

Genes affected

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

ZNF839 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF839	NM_018335.6 link	c.353T>C	p.Leu118Pro	missense_variant	Exon 2 of 8	ENST00000442396.7	NP_060805.3	A8K0R7-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF839	ENST00000442396.7 link	c.353T>C	p.Leu118Pro	missense_variant	Exon 2 of 8	5	NM_018335.6	ENSP00000399863.2	A8K0R7-5
ZNF839	ENST00000558850.5 link	c.5T>C	p.Leu2Pro	missense_variant	Exon 2 of 8	2		ENSP00000453363.1	A8K0R7-1
ZNF839	ENST00000559185.5 link	c.5T>C	p.Leu2Pro	missense_variant	Exon 2 of 8	2		ENSP00000453109.1	A8K0R7-1
ZNF839	ENST00000559098.5 link	n.161T>C		non_coding_transcript_exon_variant	Exon 2 of 9	2		ENSP00000453515.1	H0YM94

Frequencies

GnomAD3 genomes

AF:

0.335

AC:

50861

AN:

151960

Hom.:

11840

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.206

AC XY:

149820

AN XY:

726662

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

13258

26516

39774

53032

66290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7286

14572

21858

29144

36430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.335

AC:

50964

AN:

152078

Hom.:

11877

Cov.:

AF XY:

0.334

AC XY:

24814

AN XY:

74346

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.171

AC:

11612

AN:

67968

Other (OTH)

AF:

0.309

AC:

654

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1413

2826

4239

5652

7065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.031

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.0

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.0011

T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00079

LIST_S2

Benign

0.16

.;T;T

MetaRNN

Benign

0.0000083

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.6

N;N;.

PhyloP100

1.6

PrimateAI

Benign

0.29

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

GERP RS

4.2

Varity_R

0.039

gMVP

0.098

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over