Variant 8-7950731-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.302C>T(p.Ser101Phe) 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 0.000012 ( 0 hom., cov: 11)

Exomes 𝑓: 0.0000061 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

ZNF705B
NM_001193630.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.264

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=0.11111358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705B	NM_001193630.1 linkuse as main transcript	c.302C>T	p.Ser101Phe	missense_variant	6/7	ENST00000400120.3	NP_001180559.1	P0CI00
ZNF705B	XM_047421207.1 linkuse as main transcript	c.302C>T	p.Ser101Phe	missense_variant	6/7		XP_047277163.1
ZNF705B	XM_047421208.1 linkuse as main transcript	c.302C>T	p.Ser101Phe	missense_variant	4/5		XP_047277164.1
LOC124901865	use as main transcript	n.7950731C>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF705B	ENST00000400120.3 linkuse as main transcript	c.302C>T	p.Ser101Phe	missense_variant	6/7	2	NM_001193630.1	ENSP00000382987.3		P0CI00

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

84182

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000331

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000611

AC:

AN:

817736

Hom.:

Cov.:

AF XY:

0.00000491

AC XY:

AN XY:

407626

show subpopulations

Gnomad4 AFR exome

AF:

0.0000373

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000368

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000578

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000119

AC:

AN:

84182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

40138

show subpopulations

Gnomad4 AFR

AF:

0.0000331

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

ExAC

AF:

0.0000128

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

Aug 02, 2023

The c.302C>T (p.S101F) 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 302, causing the serine (S) at amino acid position 101 to be replaced by a phenylalanine (F). 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

0.16

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.2

DANN

Benign

0.80

DEOGEN2

Benign

0.10

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.00055

LIST_S2

Benign

0.39

M_CAP

Benign

0.00043

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.39

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.030

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0030

Polyphen

0.34

Vest4

0.11

MutPred

0.30

Loss of disorder (P = 0.0145);

MVP

0.043

ClinPred

0.094

GERP RS

1.0

Varity_R

0.11

gMVP

0.015

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