Variant 5-179027479-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000444149.7(ZNF879):c.40G>C(p.Val14Leu) 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 1,461,746 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: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ZNF879
ENST00000444149.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.915

Variant links:

Genes affected

ZNF879 (HGNC:37273): (zinc finger protein 879) This gene encodes a kruppel-associated box-containing zinc finger protein (KRAB-ZFP). The encoded protein contains an N-terminal kruppel-associated box (KRAB) domain and thirteen C-terminal C2H2-type zinc finger domains. The KRAB-ZFPs represent the largest family of mammalian transcriptional repressors, which function through the recruitment of the nuclear co-factor KRAB-Associated Protein 1 (KAP1), to engage histone modifiers and induce heterochromatin formation. [provided by RefSeq, Jul 2017]

ZNF879 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF879	NM_001136116.3 linkuse as main transcript	c.40G>C	p.Val14Leu	missense_variant	3/5	ENST00000444149.7	NP_001129588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF879	ENST00000444149.7 linkuse as main transcript	c.40G>C	p.Val14Leu	missense_variant	3/5	1	NM_001136116.3	ENSP00000414887	P1
ZNF879	ENST00000522442.1 linkuse as main transcript	c.40G>C	p.Val14Leu	missense_variant	3/5	4		ENSP00000428477
ZNF879	ENST00000519896.5 linkuse as main transcript	c.74G>C	p.Arg25Pro	missense_variant	3/5	4		ENSP00000430047
ZNF879	ENST00000521285.1 linkuse as main transcript	c.40G>C	p.Val14Leu	missense_variant	2/2	5		ENSP00000431043

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251030

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135686

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727150

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:

0.00000719

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

Oct 10, 2023

The c.40G>C (p.V14L) alteration is located in exon 3 (coding exon 2) of the ZNF879 gene. This alteration results from a G to C substitution at nucleotide position 40, causing the valine (V) at amino acid position 14 to be replaced by a leucine (L). 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

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.88

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.70

M_CAP

Benign

0.0058

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.25

REVEL

Benign

0.019

Sift

Benign

0.23

Sift4G

Benign

0.33

Vest4

0.29

MutPred

0.38

Loss of MoRF binding (P = 0.0015);

MVP

0.39

ClinPred

0.062

GERP RS

1.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: 32

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