5-32388365-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016107.5(ZFR):​c.2348+104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,087,008 control chromosomes in the GnomAD database, including 196,806 homozygotes. 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: 𝑓 0.63 (30451 hom., cov: 33)
  • Exomes 𝑓: 0.59 (166355 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016107.5. 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
	ZFR	NM_016107.5	MANE Select	c.2348+104A>G		intron	N/A	NP_057191.2
	ZFR	NR_144318.2		n.2430+104A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFR	ENST00000265069.13	TSL:1 MANE Select	c.2348+104A>G		intron	N/A	ENSP00000265069.8	Q96KR1
	ZFR	ENST00000956812.1		c.2348+104A>G		intron	N/A	ENSP00000626871.1
	ZFR	ENST00000890167.1		c.2372+104A>G		intron	N/A	ENSP00000560226.1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95527 AN: 152058 Hom.: 30432 Cov.: 33

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.573

GnomAD4 exome AF: 0.594 AC: 555560 AN: 934832 Hom.: 166355 AF XY: 0.592 AC XY: 278216 AN XY: 469966

African (AFR) AF: 0.721 AC: 15652 AN: 21696

American (AMR) AF: 0.603 AC: 15346 AN: 25436

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 8998 AN: 18034

East Asian (EAS) AF: 0.638 AC: 21775 AN: 34114

South Asian (SAS) AF: 0.562 AC: 32490 AN: 57844

European-Finnish (FIN) AF: 0.666 AC: 30955 AN: 46456

Middle Eastern (MID) AF: 0.436 AC: 1662 AN: 3810

European-Non Finnish (NFE) AF: 0.590 AC: 404219 AN: 685630

Other (OTH) AF: 0.585 AC: 24463 AN: 41812

GnomAD4 genome AF: 0.628 AC: 95598 AN: 152176 Hom.: 30451 Cov.: 33 AF XY: 0.628 AC XY: 46729 AN XY: 74400

African (AFR) AF: 0.722 AC: 29974 AN: 41534

American (AMR) AF: 0.594 AC: 9071 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1739 AN: 3472

East Asian (EAS) AF: 0.602 AC: 3119 AN: 5178

South Asian (SAS) AF: 0.575 AC: 2777 AN: 4828

European-Finnish (FIN) AF: 0.666 AC: 7047 AN: 10586

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39969 AN: 67976

Other (OTH) AF: 0.570 AC: 1204 AN: 2114

Alfa AF: 0.626 Hom.: 5637

Bravo AF: 0.628

Asia WGS AF: 0.543 AC: 1892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.41
DANN	Benign	0.50
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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;