Genetic Variant NM_018335.6:c.118C>A (chr14-102319883-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018335.6(ZNF839):c.118C>A(p.Gln40Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000542 in 1,291,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000035 ( 0 hom. )

Consequence

ZNF839
NM_018335.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.169

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15718886).

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.118C>A	p.Gln40Lys	missense	Exon 1 of 8	NP_060805.3	A8K0R7-5
ZNF839	NM_001385065.1		c.118C>A	p.Gln40Lys	missense	Exon 1 of 7	NP_001371994.1
ZNF839	NM_001385072.1		c.118C>A	p.Gln40Lys	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.118C>A	p.Gln40Lys	missense	Exon 1 of 8	ENSP00000399863.2	A8K0R7-5
ZNF839	ENST00000892181.1		c.118C>A	p.Gln40Lys	missense	Exon 1 of 7	ENSP00000562240.1
ZNF839	ENST00000892182.1		c.118C>A	p.Gln40Lys	missense	Exon 1 of 8	ENSP00000562241.1

Frequencies

GnomAD3 genomes

AF:

0.0000199

AC:

AN:

151072

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:

0.000586

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:

0.00000351

AC:

AN:

1139936

Hom.:

Cov.:

AF XY:

0.00000180

AC XY:

AN XY:

554268

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23340

American (AMR)

AF:

0.00

AC:

AN:

16282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17464

East Asian (EAS)

AF:

0.0000807

AC:

AN:

24774

South Asian (SAS)

AF:

0.00

AC:

AN:

38804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3118

European-Non Finnish (NFE)

AF:

0.00000106

AC:

AN:

947748

Other (OTH)

AF:

0.0000223

AC:

AN:

44890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

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:

0.0000198

AC:

AN:

151180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41408

American (AMR)

AF:

0.00

AC:

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.000588

AC:

AN:

5104

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67726

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

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

0.20

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Uncertain

(source)

DANN

Uncertain

0.98

Eigen

Benign

0.16

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.52

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

PhyloP100

0.17

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.1

REVEL

Benign

0.073

Sift

Benign

0.036

Sift4G

Benign

0.085

Polyphen

0.97

Vest4

0.18

MutPred

0.20

Gain of methylation at Q40 (P = 0.016)

MVP

0.43

MPC

0.52

ClinPred

0.66

GERP RS

2.8

PromoterAI

0.093

Neutral

(source)

gMVP

0.22

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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