11-58579536-C-T

Variant names:

• chr11-58579536-C-T
• rs924809027
• NM_053023.5:c.255C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_053023.5(ZFP91):​c.255C>T​(p.Ser85Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZFP91 NM_053023.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=1.93 with no splicing effect.

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.255C>T	p.Ser85Ser	synonymous	Exon 1 of 11	NP_444251.1	Q96JP5-1
	ZFP91	NM_001197051.2		c.255C>T	p.Ser85Ser	synonymous	Exon 1 of 11	NP_001183980.1
	ZFP91-CNTF	NR_024091.1		n.423C>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.255C>T	p.Ser85Ser	synonymous	Exon 1 of 11	ENSP00000339030.5	Q96JP5-1
	ZFP91-CNTF	ENST00000389919.8	TSL:2	n.255C>T		non_coding_transcript_exon	Exon 1 of 13	ENSP00000455911.1
	ZFP91	ENST00000870367.1		c.255C>T	p.Ser85Ser	synonymous	Exon 2 of 12	ENSP00000540426.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 193780 AF XY: 0.00

Gnomad AFR exome AF: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1426216 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 709000

African (AFR) AF: 0.00 AC: 0 AN: 29694

American (AMR) AF: 0.00 AC: 0 AN: 41180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24982

East Asian (EAS) AF: 0.00 AC: 0 AN: 35172

South Asian (SAS) AF: 0.00 AC: 0 AN: 83112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5350

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098688

Other (OTH) AF: 0.00 AC: 0 AN: 58840

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.96
PhyloP100		1.9
PromoterAI		-0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs924809027; hg19: chr11-58347009;