11-58579567-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_053023.5(ZFP91):ā€‹c.286C>Gā€‹(p.Pro96Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000278 in 1,584,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00012 ( 0 hom., cov: 31)
Exomes š‘“: 0.000018 ( 0 hom. )

Consequence

ZFP91
NM_053023.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.162
Variant links:
Genes affected
ZFP91 (HGNC:14983): (ZFP91 zinc finger protein, atypical E3 ubiquitin ligase) The protein encoded by this gene is a member of the zinc finger family of proteins. The gene product contains C2H2-type domains, which are the classical zinc finger domains found in numerous nucleic acid-binding proteins. This protein functions as a regulator of the non-canonical NF-kappaB pathway in lymphotoxin-beta receptor signaling. Alternative splicing results in multiple transcript variants. A read-through transcript variant composed of ZFP91 and the downstream CNTF gene sequence has been identified, but it is thought to be non-coding. Read-through transcription of ZFP91 and CNTF has also been observed in mouse. A ZFP91-related pseudogene has also been identified on chromosome 2. [provided by RefSeq, Oct 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.016546369).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZFP91NM_053023.5 linkuse as main transcriptc.286C>G p.Pro96Ala missense_variant 1/11 ENST00000316059.7 NP_444251.1
ZFP91-CNTFNR_024091.1 linkuse as main transcriptn.454C>G non_coding_transcript_exon_variant 1/13
ZFP91NM_001197051.2 linkuse as main transcriptc.286C>G p.Pro96Ala missense_variant 1/11 NP_001183980.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZFP91ENST00000316059.7 linkuse as main transcriptc.286C>G p.Pro96Ala missense_variant 1/111 NM_053023.5 ENSP00000339030 P1Q96JP5-1

Frequencies

GnomAD3 genomes
AF:
0.000118
AC:
18
AN:
152142
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000289
AC:
6
AN:
207288
Hom.:
0
AF XY:
0.0000173
AC XY:
2
AN XY:
115914
show subpopulations
Gnomad AFR exome
AF:
0.000532
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:
0.0000108
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000181
AC:
26
AN:
1432716
Hom.:
0
Cov.:
32
AF XY:
0.0000154
AC XY:
11
AN XY:
712878
show subpopulations
Gnomad4 AFR exome
AF:
0.000838
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:
0.00
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.000118
AC:
18
AN:
152260
Hom.:
0
Cov.:
31
AF XY:
0.0000672
AC XY:
5
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.000409
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000174
ExAC
AF:
0.0000770
AC:
9

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 submitterclinical testingAmbry GeneticsJul 27, 2021The c.286C>G (p.P96A) alteration is located in exon 1 (coding exon 1) of the ZFP91 gene. This alteration results from a C to G substitution at nucleotide position 286, causing the proline (P) at amino acid position 96 to be replaced by an alanine (A). 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
0.060
BayesDel_addAF
Benign
-0.60
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
13
DANN
Benign
0.91
DEOGEN2
Benign
0.064
T
Eigen
Benign
-0.66
Eigen_PC
Benign
-0.57
FATHMM_MKL
Benign
0.62
D
LIST_S2
Benign
0.61
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.017
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N
MutationTaster
Benign
0.93
N
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.22
N
REVEL
Benign
0.061
Sift
Benign
0.21
T
Sift4G
Benign
0.14
T
Polyphen
0.0
B
Vest4
0.073
MVP
0.068
MPC
0.21
ClinPred
0.033
T
GERP RS
0.086
Varity_R
0.033
gMVP
0.046

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: rs554176524; hg19: chr11-58347040; API