Variant 14-102326204-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018335.6(ZNF839):c.508T>C(p.Cys170Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ZNF839
NM_018335.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.570

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036438555).

BP6

Variant 14-102326204-T-C is Benign according to our data. Variant chr14-102326204-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3198744.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF839	NM_018335.6 linkuse as main transcript	c.508T>C	p.Cys170Arg	missense_variant	2/8	ENST00000442396.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF839	ENST00000442396.7 linkuse as main transcript	c.508T>C	p.Cys170Arg	missense_variant	2/8	5	NM_018335.6	A2	A8K0R7-5
ZNF839	ENST00000558850.5 linkuse as main transcript	c.160T>C	p.Cys54Arg	missense_variant	2/8	2		P2	A8K0R7-1
ZNF839	ENST00000559185.5 linkuse as main transcript	c.160T>C	p.Cys54Arg	missense_variant	2/8	2		P2	A8K0R7-1
ZNF839	ENST00000559098.5 linkuse as main transcript	c.316T>C	p.Cys106Arg	missense_variant, NMD_transcript_variant	2/9	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249058

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135122

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS 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:

0.00000547

AC:

AN:

1461584

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727050

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.1

DANN

Benign

0.64

DEOGEN2

Benign

0.0014

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.012

M_CAP

Benign

0.0093

MetaRNN

Benign

0.036

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

N;N;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.020

N;N;N

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.68

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.025

MutPred

0.21

Gain of solvent accessibility (P = 0.0055);Gain of solvent accessibility (P = 0.0055);.;

MVP

0.12

MPC

0.15

ClinPred

0.039

GERP RS

2.1

Varity_R

0.097

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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