11-58579376-G-T

Variant names:

• chr11-58579376-G-T
• NM_053023.5:c.95G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_053023.5(ZFP91):​c.95G>T​(p.Arg32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000751 in 1,331,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 7.5e-7 (0 hom.)
• Consequence: ZFP91 NM_053023.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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

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=0.06525394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP91	NM_053023.5	c.95G>T	p.Arg32Leu	missense_variant	Exon 1 of 11	ENST00000316059.7	NP_444251.1
ZFP91	NM_001197051.2	c.95G>T	p.Arg32Leu	missense_variant	Exon 1 of 11		NP_001183980.1
ZFP91-CNTF	NR_024091.1	n.263G>T		non_coding_transcript_exon_variant	Exon 1 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP91	ENST00000316059.7	c.95G>T	p.Arg32Leu	missense_variant	Exon 1 of 11	1	NM_053023.5	ENSP00000339030.5
ZFP91-CNTF	ENST00000389919.8	n.95G>T		non_coding_transcript_exon_variant	Exon 1 of 13	2		ENSP00000455911.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.51e-7 AC: 1 AN: 1331550 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 656546

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: 9.48e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.048	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.037
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.19	T
Polyphen		0.013	B
Vest4		0.15
MutPred		0.18		Gain of catalytic residue at R32 (P = 0.1882);
MVP		0.043
MPC		0.27
ClinPred		0.35	T
GERP RS		0.71
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.2
Varity_R		0.14
gMVP		0.21

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.

Other links and lift over

hg19: chr11-58346849;