Variant X-153421519-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001136273.2(ZFP92):c.1142C>T(p.Ala381Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,135,354 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 102 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., 7 hem., cov: 26)

Exomes 𝑓: 0.00024 ( 0 hom. 95 hem. )

Consequence

ZFP92
NM_001136273.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -0.545

Variant links:

Genes affected

ZFP92 (HGNC:12865): (ZFP92 zinc finger protein) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFP92 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066350102).

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP92	NM_001136273.2 linkuse as main transcript	c.1142C>T	p.Ala381Val	missense_variant	6/6	ENST00000338647.7	NP_001129745.1	A6NM28
ZFP92	NM_001386944.1 linkuse as main transcript	c.1142C>T	p.Ala381Val	missense_variant	5/5		NP_001373873.1
ZFP92	NM_001386945.1 linkuse as main transcript	c.1142C>T	p.Ala381Val	missense_variant	7/7		NP_001373874.1
ZFP92	NM_001386943.1 linkuse as main transcript	c.1016C>T	p.Ala339Val	missense_variant	4/4		NP_001373872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP92	ENST00000338647.7 linkuse as main transcript	c.1142C>T	p.Ala381Val	missense_variant	6/6	5	NM_001136273.2	ENSP00000462054.1		A6NM28

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

113449

Hom.:

Cov.:

AF XY:

0.000224

AC XY:

AN XY:

35729

show subpopulations

Gnomad AFR

AF:

0.0000955

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000734

Gnomad ASJ

AF:

0.000752

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000413

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000306

AC:

AN:

78365

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

25029

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00212

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000304

Gnomad OTH exome

AF:

0.00161

GnomAD4 exome

AF:

0.000237

AC:

242

AN:

1021859

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

AN XY:

329253

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000194

Gnomad4 ASJ exome

AF:

0.00129

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000833

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000231

Gnomad4 OTH exome

AF:

0.000394

GnomAD4 genome

AF:

0.000300

AC:

AN:

113495

Hom.:

Cov.:

AF XY:

0.000196

AC XY:

AN XY:

35785

show subpopulations

Gnomad4 AFR

AF:

0.0000953

Gnomad4 AMR

AF:

0.000733

Gnomad4 ASJ

AF:

0.000752

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000394

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000803

Hom.:

Bravo

AF:

0.000325

ExAC

AF:

0.000249

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign: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 04, 2024

The c.1142C>T (p.A381V) alteration is located in exon 4 (coding exon 4) of the ZFP92 gene. This alteration results from a C to T substitution at nucleotide position 1142, causing the alanine (A) at amino acid position 381 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

ZFP92-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 08, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.73

DANN

Benign

0.78

DEOGEN2

Benign

0.019

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.29

M_CAP

Benign

0.027

MetaRNN

Benign

0.0066

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.70

Sift4G

Uncertain

0.027

Polyphen

0.0080

Vest4

0.024

MVP

0.082

MPC

1.0

GERP RS

0.31

Varity_R

0.024

gMVP

0.12

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