Genetic Variant NM_018335.6:c.508T>C (chr14-102326204-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 3198744.Status of the report is criteria_provided_single_submitter, 1 stars.

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.508T>C	p.Cys170Arg	missense	Exon 2 of 8	NP_060805.3	A8K0R7-5
ZNF839	NM_001385065.1		c.508T>C	p.Cys170Arg	missense	Exon 2 of 7	NP_001371994.1
ZNF839	NM_001267827.2		c.160T>C	p.Cys54Arg	missense	Exon 2 of 8	NP_001254756.1	A8K0R7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF839	ENST00000442396.7	TSL:5 MANE Select	c.508T>C	p.Cys170Arg	missense	Exon 2 of 8	ENSP00000399863.2	A8K0R7-5
ZNF839	ENST00000892181.1		c.508T>C	p.Cys170Arg	missense	Exon 2 of 7	ENSP00000562240.1
ZNF839	ENST00000892182.1		c.508T>C	p.Cys170Arg	missense	Exon 2 of 8	ENSP00000562241.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

249058

AF XY:

0.00

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 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

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111776

Other (OTH)

AF:

0.00

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

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.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.048

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.1

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.0014

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.075

M_CAP

Benign

0.0093

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

PhyloP100

0.57

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.020

REVEL

Benign

0.029

Sift

Benign

0.23

Sift4G

Benign

0.68

Polyphen

0.0

Vest4

0.025

MutPred

0.21

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

Mutation Taster

=100/0

polymorphism

(source)

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

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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