chr11-58579612-C-T

Variant names:

• chr11-58579612-C-T
• NM_053023.5:c.331C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_053023.5(ZFP91):​c.331C>T​(p.Pro111Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,419,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ZFP91 NM_053023.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.18
• Publications: 0 publications found

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-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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11814222).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053023.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP91	NM_053023.5	MANE Select	c.331C>T	p.Pro111Ser	missense	Exon 1 of 11	NP_444251.1	Q96JP5-1
	ZFP91	NM_001197051.2		c.331C>T	p.Pro111Ser	missense	Exon 1 of 11	NP_001183980.1
	ZFP91-CNTF	NR_024091.1		n.499C>T		non_coding_transcript_exon	Exon 1 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP91	ENST00000316059.7	TSL:1 MANE Select	c.331C>T	p.Pro111Ser	missense	Exon 1 of 11	ENSP00000339030.5	Q96JP5-1
	ZFP91-CNTF	ENST00000389919.8	TSL:2	n.331C>T		non_coding_transcript_exon	Exon 1 of 13	ENSP00000455911.1
	ZFP91	ENST00000870367.1		c.331C>T	p.Pro111Ser	missense	Exon 2 of 12	ENSP00000540426.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1419036 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 706060

African (AFR) AF: 0.00 AC: 0 AN: 29196

American (AMR) AF: 0.00 AC: 0 AN: 38710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24574

East Asian (EAS) AF: 0.00 AC: 0 AN: 33756

South Asian (SAS) AF: 0.00 AC: 0 AN: 82812

European-Finnish (FIN) AF: 0.0000197 AC: 1 AN: 50798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5534

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095156

Other (OTH) AF: 0.00 AC: 0 AN: 58500

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.094
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.2
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.064
Sift	Benign	0.065	T
Sift4G	Benign	0.36	T
Polyphen		0.34	B
Vest4		0.29
MutPred		0.22		Gain of phosphorylation at P111 (P = 0.0357)
MVP		0.082
MPC		0.26
ClinPred		0.56	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.080
gMVP		0.057
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

hg19: chr11-58347085;