Genetic Variant ZFP92:p.Leu30Phe (chrX-153418727-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_001136273.2(ZFP92):c.88C>T(p.Leu30Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000635 in 1,166,205 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 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 0.00038 ( 0 hom., 9 hem., cov: 23)

Exomes 𝑓: 0.000030 ( 0 hom. 7 hem. )

Consequence

ZFP92
NM_001136273.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.818

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=0.021074623).

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP92	NM_001136273.2 link	c.88C>T	p.Leu30Phe	missense_variant	Exon 4 of 6	ENST00000338647.7	NP_001129745.1	A6NM28
ZFP92	NM_001386944.1 link	c.88C>T	p.Leu30Phe	missense_variant	Exon 3 of 5		NP_001373873.1
ZFP92	NM_001386945.1 link	c.88C>T	p.Leu30Phe	missense_variant	Exon 5 of 7		NP_001373874.1
ZFP92	NM_001386943.1 link	c.-39C>T		5_prime_UTR_variant	Exon 2 of 4		NP_001373872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP92	ENST00000338647.7 link	c.88C>T	p.Leu30Phe	missense_variant	Exon 4 of 6	5	NM_001136273.2	ENSP00000462054.1		A6NM28

Frequencies

GnomAD3 genomes

AF:

0.000376

AC:

AN:

111803

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

AN XY:

33973

show subpopulations

Gnomad AFR

AF:

0.00107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000377

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000669

GnomAD3 exomes

AF:

0.0000951

AC:

AN:

115718

Hom.:

AF XY:

0.0000964

AC XY:

AN XY:

41474

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.0000514

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000141

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000304

AC:

AN:

1054352

Hom.:

Cov.:

AF XY:

0.0000203

AC XY:

AN XY:

345014

show subpopulations

Gnomad4 AFR exome

AF:

0.000843

Gnomad4 AMR exome

AF:

0.000107

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000601

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000122

Gnomad4 OTH exome

AF:

0.0000900

GnomAD4 genome

AF:

0.000375

AC:

AN:

111853

Hom.:

Cov.:

AF XY:

0.000264

AC XY:

AN XY:

34033

show subpopulations

Gnomad4 AFR

AF:

0.00107

Gnomad4 AMR

AF:

0.000661

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000379

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000661

Alfa

AF:

0.000482

Hom.:

Bravo

AF:

0.000491

ESP6500AA

AF:

0.00165

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000156

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.88C>T (p.L30F) alteration is located in exon 2 (coding exon 2) of the ZFP92 gene. This alteration results from a C to T substitution at nucleotide position 88, causing the leucine (L) at amino acid position 30 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

0.16

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.042

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.30

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.021

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.34

Sift4G

Benign

0.69

Polyphen

0.44

Vest4

0.11

MVP

0.42

MPC

1.3

GERP RS

2.7

Varity_R

0.27

gMVP

0.074

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