Genetic Variant ZNF839:p.Pro59Ala (chr14-102319940-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018335.6(ZNF839):c.175C>G(p.Pro59Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000918 in 1,198,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

ZNF839
NM_018335.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17679578).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF839	NM_018335.6 link	c.175C>G	p.Pro59Ala	missense_variant	Exon 1 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.175C>G	p.Pro59Ala	missense_variant	Exon 1 of 8	5	NM_018335.6	ENSP00000399863.2	A8K0R7-5
ZNF839	ENST00000558850.5 link	c.-61+2274C>G		intron_variant	Intron 1 of 7	2		ENSP00000453363.1	A8K0R7-1
ZNF839	ENST00000559185.5 link	c.-61+422C>G		intron_variant	Intron 1 of 7	2		ENSP00000453109.1	A8K0R7-1
ZNF839	ENST00000559098.5 link	n.-18C>G		upstream_gene_variant		2		ENSP00000453515.1	H0YM94

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000858

AC:

AN:

1049184

Hom.:

Cov.:

AF XY:

0.0000118

AC XY:

AN XY:

506640

show subpopulations

Gnomad4 AFR exome

AF:

0.0000979

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000779

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149440

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72858

show subpopulations

Gnomad4 AFR

AF:

0.0000486

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.175C>G (p.P59A) alteration is located in exon 1 (coding exon 1) of the ZNF839 gene. This alteration results from a C to G substitution at nucleotide position 175, causing the proline (P) at amino acid position 59 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.4

DANN

Benign

0.64

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.34

M_CAP

Benign

0.0068

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.56

REVEL

Benign

0.078

Sift

Benign

0.21

Sift4G

Benign

0.13

Polyphen

0.93

Vest4

0.19

MutPred

0.28

Loss of loop (P = 0.0022);

MVP

0.31

MPC

0.10

ClinPred

0.48

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

gMVP

0.071

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over