Genetic Variant NM_018335.6:c.161C>T (chr14-102319926-C-T) – 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.161C>T(p.Pro54Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000085 in 1,059,206 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: not found (cov: 32)

Exomes 𝑓: 0.0000085 ( 0 hom. )

Consequence

ZNF839
NM_018335.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.261

Publications

1 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=0.087031275).

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.161C>T	p.Pro54Leu	missense	Exon 1 of 8	NP_060805.3	A8K0R7-5
ZNF839	NM_001385065.1		c.161C>T	p.Pro54Leu	missense	Exon 1 of 7	NP_001371994.1
ZNF839	NM_001385072.1		c.161C>T	p.Pro54Leu	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.161C>T	p.Pro54Leu	missense	Exon 1 of 8	ENSP00000399863.2	A8K0R7-5
ZNF839	ENST00000892181.1		c.161C>T	p.Pro54Leu	missense	Exon 1 of 7	ENSP00000562240.1
ZNF839	ENST00000892182.1		c.161C>T	p.Pro54Leu	missense	Exon 1 of 8	ENSP00000562241.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

32544

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000850

AC:

AN:

1059206

Hom.:

Cov.:

AF XY:

0.0000117

AC XY:

AN XY:

513472

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20730

American (AMR)

AF:

0.00

AC:

AN:

12106

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13680

East Asian (EAS)

AF:

0.00

AC:

AN:

18470

South Asian (SAS)

AF:

0.00

AC:

AN:

33612

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17882

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2698

European-Non Finnish (NFE)

AF:

0.0000100

AC:

AN:

900380

Other (OTH)

AF:

0.00

AC:

AN:

39648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.653

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.58

M_CAP

Benign

0.021

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.0

PhyloP100

0.26

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.4

REVEL

Benign

0.026

Sift

Benign

0.23

Sift4G

Uncertain

0.013

Polyphen

0.18

Vest4

0.25

MutPred

0.23

Gain of catalytic residue at P55 (P = 5e-04)

MVP

0.26

MPC

0.10

ClinPred

0.86

GERP RS

1.3

PromoterAI

-0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

gMVP

0.12

Mutation Taster

=261/39

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

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