rs561077533

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018335.6(ZNF839):c.2093G>A(p.Arg698Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,597,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R698W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ZNF839
NM_018335.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.63

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:

CINP (HGNC:23789): (cyclin dependent kinase 2 interacting protein) The protein encoded by this gene is reported to be a component of the DNA replication complex as well as a genome-maintenance protein. It may interact with proteins important for replication initiation and has been shown to bind chromatin at the G1 phase of the cell cycle and dissociate from chromatin with replication initiation. It may also serve to regulate checkpoint signaling as part of the DNA damage response. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

CINP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028910518).

BP6

Variant 14-102341488-G-A is Benign according to our data. Variant chr14-102341488-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2468345.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2093G>A	p.Arg698Gln	missense	Exon 8 of 8	NP_060805.3	A8K0R7-5
ZNF839	NM_001385065.1		c.1943G>A	p.Arg648Gln	missense	Exon 7 of 7	NP_001371994.1
ZNF839	NM_001267827.2		c.1745G>A	p.Arg582Gln	missense	Exon 8 of 8	NP_001254756.1	A8K0R7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF839	ENST00000442396.7	TSL:5 MANE Select	c.2093G>A	p.Arg698Gln	missense	Exon 8 of 8	ENSP00000399863.2	A8K0R7-5
ZNF839	ENST00000557803.5	TSL:1	n.1340G>A		non_coding_transcript_exon	Exon 4 of 4
ZNF839	ENST00000892181.1		c.2000G>A	p.Arg667Gln	missense	Exon 7 of 7	ENSP00000562240.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000127

AC:

AN:

237014

AF XY:

0.0000156

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000562

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

1445518

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

717248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33094

American (AMR)

AF:

0.00

AC:

AN:

42844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25058

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39410

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.0000127

AC:

AN:

1102462

Other (OTH)

AF:

0.0000336

AC:

AN:

59544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.0000131

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.067

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.0060

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.00082

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0072

LIST_S2

Benign

0.46

M_CAP

Benign

0.0016

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

PhyloP100

-1.6

PrimateAI

Benign

0.28

PROVEAN

Benign

1.7

REVEL

Benign

0.011

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.029

MutPred

0.21

Loss of stability (P = 0.024)

MVP

0.085

MPC

0.10

ClinPred

0.022

GERP RS

-9.0

Varity_R

0.0095

gMVP

0.097

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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