Variant 14-102319937-C-T 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.172C>T(p.Pro58Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000945 in 1,058,236 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: not found (cov: 32)

Exomes 𝑓: 9.4e-7 ( 0 hom. )

Consequence

ZNF839
NM_018335.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

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:

ZNF839 (HGNC:):

ZNF839 links:

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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=0.09925106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF839	NM_018335.6 linkuse as main transcript	c.172C>T	p.Pro58Ser	missense_variant	1/8	ENST00000442396.7	NP_060805.3	A8K0R7-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF839	ENST00000442396.7 linkuse as main transcript	c.172C>T	p.Pro58Ser	missense_variant	1/8	5	NM_018335.6	ENSP00000399863.2	A8K0R7-5
ZNF839	ENST00000558850.5 linkuse as main transcript	c.-61+2271C>T		intron_variant		2		ENSP00000453363.1	A8K0R7-1
ZNF839	ENST00000559185.5 linkuse as main transcript	c.-61+419C>T		intron_variant		2		ENSP00000453109.1	A8K0R7-1
ZNF839	ENST00000559098.5 linkuse as main transcript	n.-21C>T		upstream_gene_variant		2		ENSP00000453515.1	H0YM94

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000382

AC:

AN:

26182

Hom.:

AF XY:

0.00

AC XY:

AN XY:

16086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.45e-7

AC:

AN:

1058236

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

512182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000111

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 07, 2021

The c.172C>T (p.P58S) alteration is located in exon 1 (coding exon 1) of the ZNF839 gene. This alteration results from a C to T substitution at nucleotide position 172, causing the proline (P) at amino acid position 58 to be replaced by a serine (S). 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

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.93

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.34

M_CAP

Benign

0.045

MetaRNN

Benign

0.099

MetaSVM

Benign

-0.97

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.74

REVEL

Benign

0.020

Sift

Benign

0.83

Sift4G

Benign

0.44

Polyphen

0.75

Vest4

0.29

MutPred

0.26

Gain of catalytic residue at P53 (P = 5e-04);

MVP

0.29

MPC

0.44

ClinPred

0.11

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

gMVP

0.14

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