chr11-58579567-C-G

Variant names:

• chr11-58579567-C-G
• rs554176524
• NM_053023.5:c.286C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_053023.5(ZFP91):​c.286C>G​(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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: ZFP91 NM_053023.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.162
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.016546369).

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.286C>G	p.Pro96Ala	missense	Exon 1 of 11	NP_444251.1	Q96JP5-1
	ZFP91	NM_001197051.2		c.286C>G	p.Pro96Ala	missense	Exon 1 of 11	NP_001183980.1
	ZFP91-CNTF	NR_024091.1		n.454C>G		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.286C>G	p.Pro96Ala	missense	Exon 1 of 11	ENSP00000339030.5	Q96JP5-1
	ZFP91-CNTF	ENST00000389919.8	TSL:2	n.286C>G		non_coding_transcript_exon	Exon 1 of 13	ENSP00000455911.1
	ZFP91	ENST00000870367.1		c.286C>G	p.Pro96Ala	missense	Exon 2 of 12	ENSP00000540426.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152142 Hom.: 0 Cov.: 31

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

GnomAD2 exomes AF: 0.0000289 AC: 6 AN: 207288 AF XY: 0.0000173

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 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

African (AFR) AF: 0.000838 AC: 25 AN: 29834

American (AMR) AF: 0.00 AC: 0 AN: 41800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25066

East Asian (EAS) AF: 0.00 AC: 0 AN: 35258

South Asian (SAS) AF: 0.00 AC: 0 AN: 84116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5592

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100898

Other (OTH) AF: 0.0000169 AC: 1 AN: 59128

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152260 Hom.: 0 Cov.: 31 AF XY: 0.0000672 AC XY: 5 AN XY: 74456

African (AFR) AF: 0.000409 AC: 17 AN: 41564

American (AMR) AF: 0.0000654 AC: 1 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000174

ExAC AF: 0.0000770 AC: 9

ClinVar

ClinVar submissions as Germline

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	0.060
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
PhyloP100		-0.16
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
Mutation Taster		=95/5	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

dbSNP: rs554176524; hg19: chr11-58347040;