Variant X-153421588-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.1211C>T(p.Pro404Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000271 in 1,033,164 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 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 0.00012 ( 0 hom., 3 hem., cov: 26)

Exomes 𝑓: 0.000016 ( 0 hom. 6 hem. )

Consequence

ZFP92
NM_001136273.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0530

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=0.0077941716).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZFP92	NM_001136273.2 linkuse as main transcript	c.1211C>T	p.Pro404Leu	missense_variant	6/6	ENST00000338647.7	NP_001129745.1
ZFP92	NM_001386944.1 linkuse as main transcript	c.1211C>T	p.Pro404Leu	missense_variant	5/5		NP_001373873.1
ZFP92	NM_001386945.1 linkuse as main transcript	c.1211C>T	p.Pro404Leu	missense_variant	7/7		NP_001373874.1
ZFP92	NM_001386943.1 linkuse as main transcript	c.1085C>T	p.Pro362Leu	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.1211C>T	p.Pro404Leu	missense_variant	6/6	5	NM_001136273.2	ENSP00000462054	P1

Frequencies

GnomAD3 genomes

AF:

0.000115

AC:

AN:

112954

Hom.:

Cov.:

AF XY:

0.0000850

AC XY:

AN XY:

35304

show subpopulations

Gnomad AFR

AF:

0.000383

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000812

AC:

AN:

12320

Hom.:

AF XY:

0.00

AC XY:

AN XY:

1772

show subpopulations

Gnomad AFR exome

AF:

0.00385

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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

AF:

0.0000163

AC:

AN:

920210

Hom.:

Cov.:

AF XY:

0.0000209

AC XY:

AN XY:

287130

show subpopulations

Gnomad4 AFR exome

AF:

0.000164

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000919

Gnomad4 OTH exome

AF:

0.0000793

GnomAD4 genome

AF:

0.000115

AC:

AN:

112954

Hom.:

Cov.:

AF XY:

0.0000850

AC XY:

AN XY:

35304

show subpopulations

Gnomad4 AFR

AF:

0.000383

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:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000147

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.000231

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

Oct 04, 2022

The c.1211C>T (p.P404L) 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 1211, causing the proline (P) at amino acid position 404 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.042

DANN

Benign

0.77

DEOGEN2

Benign

0.0080

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.37

M_CAP

Benign

0.040

MetaRNN

Benign

0.0078

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

Sift4G

Benign

0.31

Polyphen

0.0

Vest4

0.11

MVP

0.068

MPC

1.0

GERP RS

-3.9

Varity_R

0.039

gMVP

0.26

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