Variant 5-179032358-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001136116.3(ZNF879):c.410T>G(p.Leu137Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF879
NM_001136116.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.304

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04142946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF879	NM_001136116.3 linkuse as main transcript	c.410T>G	p.Leu137Arg	missense_variant	5/5	ENST00000444149.7	NP_001129588.1	B4DU55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF879	ENST00000444149.7 linkuse as main transcript	c.410T>G	p.Leu137Arg	missense_variant	5/5	1	NM_001136116.3	ENSP00000414887.2	B4DU55
ZNF879	ENST00000522442.1 linkuse as main transcript	c.*6T>G		downstream_gene_variant		4		ENSP00000428477.1	E5RI37
ZNF879	ENST00000519896.5 linkuse as main transcript	c.*120T>G		downstream_gene_variant		4		ENSP00000430047.1	E5RGZ8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000652

AC:

AN:

153424

Hom.:

AF XY:

0.00

AC XY:

AN XY:

81390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000919

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

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000756

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

Apr 07, 2023

The c.410T>G (p.L137R) alteration is located in exon 5 (coding exon 4) of the ZNF879 gene. This alteration results from a T to G substitution at nucleotide position 410, causing the leucine (L) at amino acid position 137 to be replaced by an arginine (R). 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

Benign

0.075

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.0073

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.00024

M_CAP

Benign

0.0045

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.23

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.1

REVEL

Benign

0.043

Sift

Benign

0.37

Sift4G

Benign

0.37

Polyphen

0.037

Vest4

0.13

MVP

0.081

MPC

0.25

ClinPred

0.019

GERP RS

1.1

Varity_R

0.065

gMVP

0.17

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