Variant 8-7950092-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001193630.1(ZNF705B):c.199T>C(p.Trp67Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00095 ( 0 hom., cov: 9)

Exomes 𝑓: 0.000034 ( 6 hom. )

Failed GnomAD Quality Control

Consequence

ZNF705B
NM_001193630.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.842

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011075944).

BP6

Variant 8-7950092-T-C is Benign according to our data. Variant chr8-7950092-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2346906.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705B	NM_001193630.1 linkuse as main transcript	c.199T>C	p.Trp67Arg	missense_variant	5/7	ENST00000400120.3	NP_001180559.1	P0CI00
ZNF705B	XM_047421207.1 linkuse as main transcript	c.199T>C	p.Trp67Arg	missense_variant	5/7		XP_047277163.1
ZNF705B	XM_047421208.1 linkuse as main transcript	c.199T>C	p.Trp67Arg	missense_variant	3/5		XP_047277164.1
LOC124901865	use as main transcript	n.7950092T>C		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF705B	ENST00000400120.3 linkuse as main transcript	c.199T>C	p.Trp67Arg	missense_variant	5/7	2	NM_001193630.1	ENSP00000382987.3		P0CI00

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

68668

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000456

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:

0.00125

GnomAD3 exomes

AF:

0.000224

AC:

AN:

134066

Hom.:

AF XY:

0.000232

AC XY:

AN XY:

73276

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.000482

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:

0.0000166

Gnomad OTH exome

AF:

0.000293

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000342

AC:

AN:

994510

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

495262

show subpopulations

Gnomad4 AFR exome

AF:

0.000651

Gnomad4 AMR exome

AF:

0.000374

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:

0.00000129

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000945

AC:

AN:

68752

Hom.:

Cov.:

AF XY:

0.000896

AC XY:

AN XY:

32354

show subpopulations

Gnomad4 AFR

AF:

0.00233

Gnomad4 AMR

AF:

0.000456

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:

0.00123

Alfa

AF:

0.00261

Hom.:

ExAC

AF:

0.0000535

AC:

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

Oct 27, 2021

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

Uncertain

0.48

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.35

DANN

Benign

0.40

DEOGEN2

Benign

0.0074

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.0025

M_CAP

Benign

0.0013

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.2

PrimateAI

Uncertain

0.60

PROVEAN

Benign

1.5

REVEL

Benign

0.019

Sift

Benign

0.54

Sift4G

Benign

0.42

Polyphen

0.0

Vest4

0.035

MutPred

0.42

Loss of catalytic residue at L65 (P = 0.0047);

MVP

0.043

ClinPred

0.0044

GERP RS

-1.1

Varity_R

0.070

gMVP

0.017

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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