Variant X-153421516-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.1139C>T(p.Thr380Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000965 in 1,139,403 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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 0.000018 ( 0 hom., 1 hem., cov: 26)

Exomes 𝑓: 0.0000088 ( 0 hom. 3 hem. )

Consequence

ZFP92
NM_001136273.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.12

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=0.045220703).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZFP92	NM_001136273.2 linkuse as main transcript	c.1139C>T	p.Thr380Met	missense_variant	6/6	ENST00000338647.7
ZFP92	NM_001386944.1 linkuse as main transcript	c.1139C>T	p.Thr380Met	missense_variant	5/5
ZFP92	NM_001386945.1 linkuse as main transcript	c.1139C>T	p.Thr380Met	missense_variant	7/7
ZFP92	NM_001386943.1 linkuse as main transcript	c.1013C>T	p.Thr338Met	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP92	ENST00000338647.7 linkuse as main transcript	c.1139C>T	p.Thr380Met	missense_variant	6/6	5	NM_001136273.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0000176

AC:

AN:

113483

Hom.:

Cov.:

AF XY:

0.0000280

AC XY:

AN XY:

35751

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000877

AC:

AN:

1025874

Hom.:

Cov.:

AF XY:

0.00000904

AC XY:

AN XY:

331824

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000388

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000985

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000176

AC:

AN:

113529

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

35807

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Jan 23, 2023

The c.1139C>T (p.T380M) 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 1139, causing the threonine (T) at amino acid position 380 to be replaced by a methionine (M). 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

0.14

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.55

DANN

Benign

0.77

DEOGEN2

Benign

0.011

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.17

M_CAP

Benign

0.026

MetaRNN

Benign

0.045

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

Sift4G

Benign

0.073

Polyphen

0.97

Vest4

0.14

MVP

0.10

MPC

1.3

GERP RS

-2.3

Varity_R

0.019

gMVP

0.14

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