Variant X-153421312-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001136273.2(ZFP92):c.935G>A(p.Arg312His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,167,608 control chromosomes in the GnomAD database, including 1 homozygotes. There are 14 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000036 ( 1 hom., 0 hem., cov: 27)

Exomes 𝑓: 0.000023 ( 0 hom. 14 hem. )

Consequence

ZFP92
NM_001136273.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.275

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07635316).

BS2

High Hemizygotes in GnomAdExome4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZFP92	NM_001136273.2 linkuse as main transcript	c.935G>A	p.Arg312His	missense_variant	6/6	ENST00000338647.7	NP_001129745.1
ZFP92	NM_001386944.1 linkuse as main transcript	c.935G>A	p.Arg312His	missense_variant	5/5		NP_001373873.1
ZFP92	NM_001386945.1 linkuse as main transcript	c.935G>A	p.Arg312His	missense_variant	7/7		NP_001373874.1
ZFP92	NM_001386943.1 linkuse as main transcript	c.809G>A	p.Arg270His	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.935G>A	p.Arg312His	missense_variant	6/6	5	NM_001136273.2	ENSP00000462054	P1

Frequencies

GnomAD3 genomes

AF:

0.0000359

AC:

AN:

111547

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34315

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:

0.00108

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000619

AC:

AN:

113116

Hom.:

AF XY:

0.000136

AC XY:

AN XY:

36664

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:

0.000480

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000227

AC:

AN:

1056016

Hom.:

Cov.:

AF XY:

0.0000408

AC XY:

AN XY:

343176

show subpopulations

Gnomad4 AFR exome

AF:

0.0000399

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000456

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000358

AC:

AN:

111592

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34370

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:

0.00109

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000190

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000571

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

Feb 16, 2023

The c.935G>A (p.R312H) alteration is located in exon 4 (coding exon 4) of the ZFP92 gene. This alteration results from a G to A substitution at nucleotide position 935, causing the arginine (R) at amino acid position 312 to be replaced by a histidine (H). 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

Pathogenic

0.73

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.19

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.29

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.076

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.046

MVP

0.51

MPC

1.3

GERP RS

0.19

Varity_R

0.049

gMVP

0.56

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