Variant 8-7357992-G-A 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_001164457.3(ZNF705G):c.887C>T(p.Ser296Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 149,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 38)

Consequence

ZNF705G
NM_001164457.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.90

Variant links:

Genes affected

ZNF705G (HGNC:37134): (zinc finger protein 705G) 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]

ZNF705G 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=0.06100133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF705G	NM_001164457.3 linkuse as main transcript	c.887C>T	p.Ser296Phe	missense_variant	7/7	ENST00000400156.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF705G	ENST00000400156.4 linkuse as main transcript	c.887C>T	p.Ser296Phe	missense_variant	7/7	2	NM_001164457.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149716

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

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:

0.00000401

AC:

AN:

249072

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135304

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

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.:

152

GnomAD4 genome

AF:

0.0000133

AC:

AN:

149836

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Dec 02, 2022

The c.887C>T (p.S296F) alteration is located in exon 5 (coding exon 5) of the ZNF705G gene. This alteration results from a C to T substitution at nucleotide position 887, causing the serine (S) at amino acid position 296 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

0.31

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

Cadd

Benign

0.52

Dann

Benign

0.40

DEOGEN2

Benign

0.081

Eigen

Benign

-0.88

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.70

M_CAP

Benign

0.0022

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.088

Sift

Benign

0.097

Sift4G

Benign

0.64

Vest4

0.087

MVP

0.32

MPC

0.0012

ClinPred

0.21

GERP RS

-0.20

Varity_R

0.058

gMVP

0.0054

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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