Genetic Variant ZNF839:p.Glu46Gln (chr14-102319901-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018335.6(ZNF839):c.136G>C(p.Glu46Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,272,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ZNF839
NM_018335.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.34

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16668737).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF839	NM_018335.6	MANE Select	c.136G>C	p.Glu46Gln	missense	Exon 1 of 8	NP_060805.3	A8K0R7-5
ZNF839	NM_001385065.1		c.136G>C	p.Glu46Gln	missense	Exon 1 of 7	NP_001371994.1
ZNF839	NM_001385072.1		c.136G>C	p.Glu46Gln	missense	Exon 1 of 8	NP_001372001.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF839	ENST00000442396.7	TSL:5 MANE Select	c.136G>C	p.Glu46Gln	missense	Exon 1 of 8	ENSP00000399863.2	A8K0R7-5
ZNF839	ENST00000892181.1		c.136G>C	p.Glu46Gln	missense	Exon 1 of 7	ENSP00000562240.1
ZNF839	ENST00000892182.1		c.136G>C	p.Glu46Gln	missense	Exon 1 of 8	ENSP00000562241.1

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

150538

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1121360

Hom.:

Cov.:

AF XY:

0.0000201

AC XY:

AN XY:

546068

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22462

American (AMR)

AF:

0.0000613

AC:

AN:

16310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16526

East Asian (EAS)

AF:

0.00

AC:

AN:

22838

South Asian (SAS)

AF:

0.00

AC:

AN:

39348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3024

European-Non Finnish (NFE)

AF:

0.0000235

AC:

AN:

936128

Other (OTH)

AF:

0.00

AC:

AN:

43498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000199

AC:

AN:

150650

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73588

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41324

American (AMR)

AF:

0.000198

AC:

AN:

15164

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5080

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67560

Other (OTH)

AF:

0.00

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

0.16

Eigen_PC

Benign

0.052

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.55

M_CAP

Benign

0.049

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

PhyloP100

1.3

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.82

REVEL

Benign

0.081

Sift

Uncertain

0.028

Sift4G

Uncertain

0.025

Polyphen

1.0

Vest4

0.084

MutPred

0.14

Gain of MoRF binding (P = 0.0326)

MVP

0.31

MPC

0.35

ClinPred

0.75

GERP RS

0.69

PromoterAI

-0.066

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

gMVP

0.20

Mutation Taster

=88/12

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over