Variant 8-7950099-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001193630.1(ZNF705B):c.206G>A(p.Gly69Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 9)

Exomes 𝑓: 0.000064 ( 17 hom. )

Failed GnomAD Quality Control

Consequence

ZNF705B
NM_001193630.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.180

Variant links:

Genes affected

ZNF705B (HGNC:32284): (zinc finger protein 705B) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF705B links:

LOC124901865 (HGNC:):

LOC124901865 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.060986727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705B	NM_001193630.1 linkuse as main transcript	c.206G>A	p.Gly69Glu	missense_variant	5/7	ENST00000400120.3	NP_001180559.1	P0CI00
ZNF705B	XM_047421207.1 linkuse as main transcript	c.206G>A	p.Gly69Glu	missense_variant	5/7		XP_047277163.1
ZNF705B	XM_047421208.1 linkuse as main transcript	c.206G>A	p.Gly69Glu	missense_variant	3/5		XP_047277164.1
LOC124901865	use as main transcript	n.7950099G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF705B	ENST00000400120.3 linkuse as main transcript	c.206G>A	p.Gly69Glu	missense_variant	5/7	2	NM_001193630.1	ENSP00000382987.3		P0CI00

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

68552

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000119

AC:

AN:

134046

Hom.:

AF XY:

0.000136

AC XY:

AN XY:

73264

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:

0.0000521

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000215

Gnomad OTH exome

AF:

0.000588

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000638

AC:

AN:

846080

Hom.:

Cov.:

AF XY:

0.0000876

AC XY:

AN XY:

422370

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:

0.0000909

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000713

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

68552

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32208

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000822

AC:

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

May 16, 2023

The c.206G>A (p.G69E) alteration is located in exon 5 (coding exon 3) of the ZNF705B gene. This alteration results from a G to A substitution at nucleotide position 206, causing the glycine (G) at amino acid position 69 to be replaced by a glutamic acid (E). 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

0.27

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.78

CADD

Benign

9.0

DANN

Benign

0.69

DEOGEN2

Benign

0.0077

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.13

M_CAP

Benign

0.0020

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.095

PrimateAI

Uncertain

0.65

PROVEAN

Benign

1.2

REVEL

Benign

0.055

Sift

Benign

1.0

Sift4G

Benign

0.73

Polyphen

0.98

Vest4

0.12

MutPred

0.46

Gain of disorder (P = 0.1798);

MVP

0.043

ClinPred

0.048

GERP RS

-0.58

Varity_R

0.17

gMVP

0.014

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