Variant chr11-58579520-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_053023.5(ZFP91):c.239G>A(p.Arg80Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,411,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZFP91
NM_053023.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.85

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]

ZFP91 links:

ZFP91-CNTF (HGNC:33441): (ZFP91-CNTF readthrough (NMD candidate)) This gene represents a read-through transcript composed of ZFP91 and CNTF sequence. This transcript is thought to be non-coding because it would be subject to nonsense-mediated mRNA decay (NMD). Read-through transcription of ZFP91 and CNTF has also been observed in mouse. [provided by RefSeq, Aug 2008]

ZFP91-CNTF links:

ZFP91-CNTF (HGNC:):

ZFP91-CNTF links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19349483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZFP91	NM_053023.5 linkuse as main transcript	c.239G>A	p.Arg80Gln	missense_variant	1/11	ENST00000316059.7	NP_444251.1
ZFP91	NM_001197051.2 linkuse as main transcript	c.239G>A	p.Arg80Gln	missense_variant	1/11		NP_001183980.1
ZFP91-CNTF	NR_024091.1 linkuse as main transcript	n.407G>A		non_coding_transcript_exon_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP91	ENST00000316059.7 linkuse as main transcript	c.239G>A	p.Arg80Gln	missense_variant	1/11	1	NM_053023.5	ENSP00000339030.5		Q96JP5-1
ZFP91-CNTF	ENST00000389919.8 linkuse as main transcript	n.239G>A		non_coding_transcript_exon_variant	1/13	2		ENSP00000455911.1		A0A0A6YYC7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1411808

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701058

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000275

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 06, 2024

The c.239G>A (p.R80Q) alteration is located in exon 1 (coding exon 1) of the ZFP91 gene. This alteration results from a G to A substitution at nucleotide position 239, causing the arginine (R) at amino acid position 80 to be replaced by a glutamine (Q). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.049

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.51

REVEL

Benign

0.095

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.045

Polyphen

0.98

Vest4

0.27

MutPred

0.12

Loss of MoRF binding (P = 0.0626);

MVP

0.15

MPC

0.25

ClinPred

0.76

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.42

gMVP

0.11

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over