Variant 14-102319901-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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. 11/18 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

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=0.16668737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF839	NM_018335.6 linkuse as main transcript	c.136G>C	p.Glu46Gln	missense_variant	1/8	ENST00000442396.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF839	ENST00000442396.7 linkuse as main transcript	c.136G>C	p.Glu46Gln	missense_variant	1/8	5	NM_018335.6	A2	A8K0R7-5
ZNF839	ENST00000558850.5 linkuse as main transcript	c.-61+2235G>C		intron_variant		2		P2	A8K0R7-1
ZNF839	ENST00000559185.5 linkuse as main transcript	c.-61+383G>C		intron_variant		2		P2	A8K0R7-1

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000613

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:

0.0000235

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000199

AC:

AN:

150650

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73588

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000198

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.136G>C (p.E46Q) alteration is located in exon 1 (coding exon 1) of the ZNF839 gene. This alteration results from a G to C substitution at nucleotide position 136, causing the glutamic acid (E) at amino acid position 46 to be replaced by a glutamine (Q). 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

-0.35

BayesDel_noAF

Benign

-0.73

CADD

Benign

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

MutationTaster

Benign

1.0

D;D;D;N

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

gMVP

0.20

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