X-153418727-C-T

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

2
11

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]

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
ZFP92NM_001136273.2 linkc.88C>T p.Leu30Phe missense_variant Exon 4 of 6 ENST00000338647.7 NP_001129745.1 A6NM28
ZFP92NM_001386944.1 linkc.88C>T p.Leu30Phe missense_variant Exon 3 of 5 NP_001373873.1
ZFP92NM_001386945.1 linkc.88C>T p.Leu30Phe missense_variant Exon 5 of 7 NP_001373874.1
ZFP92NM_001386943.1 linkc.-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
ZFP92ENST00000338647.7 linkc.88C>T p.Leu30Phe missense_variant Exon 4 of 6 5 NM_001136273.2 ENSP00000462054.1 A6NM28

Frequencies

GnomAD3 genomes
AF:
0.000376
AC:
42
AN:
111803
Hom.:
0
Cov.:
23
AF XY:
0.000265
AC XY:
9
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:
11
AN:
115718
Hom.:
0
AF XY:
0.0000964
AC XY:
4
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:
32
AN:
1054352
Hom.:
0
Cov.:
31
AF XY:
0.0000203
AC XY:
7
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:
42
AN:
111853
Hom.:
0
Cov.:
23
AF XY:
0.000264
AC XY:
9
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.:
2
Bravo
AF:
0.000491
ESP6500AA
AF:
0.00165
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000156
AC:
4

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
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.042
T
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.30
T
M_CAP
Uncertain
0.28
D
MetaRNN
Benign
0.021
T
MutationAssessor
Uncertain
2.7
M
PrimateAI
Benign
0.34
T
Sift4G
Benign
0.69
T
Polyphen
0.44
B
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.

Other links and lift over

dbSNP: rs376108579; hg19: chrX-152684185; API