NM_053023.5:c.43G>A

Variant names:

• chr11-58579324-G-A
• rs1464232884
• NM_053023.5:c.43G>A

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.43G>A​(p.Asp15Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000535 in 1,494,200 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: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: ZFP91 NM_053023.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34
• Publications: 1 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=0.08082488).

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.43G>A	p.Asp15Asn	missense	Exon 1 of 11	NP_444251.1	Q96JP5-1
	ZFP91	NM_001197051.2		c.43G>A	p.Asp15Asn	missense	Exon 1 of 11	NP_001183980.1
	ZFP91-CNTF	NR_024091.1		n.211G>A		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.43G>A	p.Asp15Asn	missense	Exon 1 of 11	ENSP00000339030.5	Q96JP5-1
	ZFP91-CNTF	ENST00000389919.8	TSL:2	n.43G>A		non_coding_transcript_exon	Exon 1 of 13	ENSP00000455911.1
	ZFP91	ENST00000870367.1		c.43G>A	p.Asp15Asn	missense	Exon 2 of 12	ENSP00000540426.1

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151756 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000968

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome AF: 0.00000298 AC: 4 AN: 1342444 Hom.: 0 Cov.: 31 AF XY: 0.00000302 AC XY: 2 AN XY: 661982

African (AFR) AF: 0.000113 AC: 3 AN: 26566

American (AMR) AF: 0.00 AC: 0 AN: 28034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23208

East Asian (EAS) AF: 0.00 AC: 0 AN: 29530

South Asian (SAS) AF: 0.00 AC: 0 AN: 74572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 9.45e-7 AC: 1 AN: 1058494

Other (OTH) AF: 0.00 AC: 0 AN: 55474

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151756 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74104

African (AFR) AF: 0.0000968 AC: 4 AN: 41342

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5108

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67856

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.3
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.037
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.084	T
Polyphen		0.069	B
Vest4		0.19
MutPred		0.15		Loss of helix (P = 0.0558)
MVP		0.068
MPC		0.21
ClinPred		0.62	D
GERP RS		2.3
PromoterAI		0.061	Neutral
Varity_R		0.29
gMVP		0.15
Mutation Taster		=89/11	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: rs1464232884; hg19: chr11-58346797;