Variant 8-7950743-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001193630.1(ZNF705B):c.314C>T(p.Thr105Ile) 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: not found (cov: 11)

Exomes 𝑓: 0.0000025 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

ZNF705B
NM_001193630.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.163

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.070102096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705B	NM_001193630.1 linkuse as main transcript	c.314C>T	p.Thr105Ile	missense_variant	6/7	ENST00000400120.3	NP_001180559.1	P0CI00
ZNF705B	XM_047421207.1 linkuse as main transcript	c.314C>T	p.Thr105Ile	missense_variant	6/7		XP_047277163.1
ZNF705B	XM_047421208.1 linkuse as main transcript	c.314C>T	p.Thr105Ile	missense_variant	4/5		XP_047277164.1
LOC124901865	use as main transcript	n.7950743C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF705B	ENST00000400120.3 linkuse as main transcript	c.314C>T	p.Thr105Ile	missense_variant	6/7	2	NM_001193630.1	ENSP00000382987.3		P0CI00

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000144

AC:

AN:

138870

Hom.:

AF XY:

0.0000266

AC XY:

AN XY:

75282

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:

0.0000329

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000245

AC:

AN:

815250

Hom.:

Cov.:

AF XY:

0.00000492

AC XY:

AN XY:

406386

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:

0.00000327

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

Sep 17, 2021

The c.314C>T (p.T105I) alteration is located in exon 6 (coding exon 4) of the ZNF705B gene. This alteration results from a C to T substitution at nucleotide position 314, causing the threonine (T) at amino acid position 105 to be replaced by an isoleucine (I). 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

0.12

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.0

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Benign

-0.91

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0058

LIST_S2

Benign

0.46

M_CAP

Benign

0.0010

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.030

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.4

REVEL

Benign

0.029

Sift

Benign

0.18

Sift4G

Benign

0.23

Polyphen

0.51

Vest4

0.10

MutPred

0.19

Gain of catalytic residue at L110 (P = 0.0419);

MVP

0.043

ClinPred

0.085

GERP RS

1.0

Varity_R

0.046

gMVP

0.026

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