rs889318

Variant names:

• chr5-32388365-T-A
• rs889318
• NM_016107.5:c.2348+104A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-32388365-T-A
• chr5-32388365-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016107.5(ZFR):​c.2348+104A>T variant causes a intron 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZFR NM_016107.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 3 publications found

Genes affected

ZFR (HGNC:17277): (zinc finger RNA binding protein) This gene encodes an RNA-binding protein characterized by its DZF (domain associated with zinc fingers) domain. The encoded protein may play a role in the nucleocytoplasmic shuttling of another RNA-binding protein, Staufen homolog 2, in neurons. Expression of this gene is regulated through alternative polyadenylation that mediates differential microRNA targeting. Elevated expression of this gene has been observed in human patients with pancreatic cancer and knockdown of this gene may result in reduced viability and invasion of pancreatic cancer cells. [provided by RefSeq, Sep 2016]

ZFR Gene-Disease associations (from GenCC):

• autosomal recessive spastic paraplegia type 71

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary spastic paraplegia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFR	NM_016107.5	c.2348+104A>T		intron_variant	Intron 13 of 19	ENST00000265069.13	NP_057191.2
ZFR	NR_144318.2	n.2430+104A>T		intron_variant	Intron 13 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFR	ENST00000265069.13	c.2348+104A>T		intron_variant	Intron 13 of 19	1	NM_016107.5	ENSP00000265069.8
ZFR	ENST00000507465.1	n.248+104A>T		intron_variant	Intron 2 of 7	5		ENSP00000422300.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 937414 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 471232

African (AFR) AF: 0.00 AC: 0 AN: 21744

American (AMR) AF: 0.00 AC: 0 AN: 25482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18076

East Asian (EAS) AF: 0.00 AC: 0 AN: 34166

South Asian (SAS) AF: 0.00 AC: 0 AN: 57956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3830

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 687750

Other (OTH) AF: 0.00 AC: 0 AN: 41892

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 5637

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.26
DANN	Benign	0.65
PhyloP100		-1.4

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: rs889318; hg19: chr5-32388471;