5-32439218-A-G

Variant names:

• chr5-32439218-A-G
• rs641221
• NM_016107.5:c.137+5011T>C

Variant summary

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

The NM_016107.5(ZFR):​c.137+5011T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,002 control chromosomes in the GnomAD database, including 13,438 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 0.42 (13438 hom., cov: 32)
• Consequence: ZFR NM_016107.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.754
• Publications: 0 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFR	NM_016107.5	MANE Select	c.137+5011T>C		intron	N/A	NP_057191.2
	ZFR	NR_144318.2		n.219+5011T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFR	ENST00000265069.13	TSL:1 MANE Select	c.137+5011T>C		intron	N/A	ENSP00000265069.8
	ZFR	ENST00000505366.1	TSL:1	n.217+5011T>C		intron	N/A
	ZFR	ENST00000505204.1	TSL:4	n.268+5011T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63453 AN: 151884 Hom.: 13439 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.418 AC: 63483 AN: 152002 Hom.: 13438 Cov.: 32 AF XY: 0.420 AC XY: 31170 AN XY: 74296

African (AFR) AF: 0.358 AC: 14858 AN: 41446

American (AMR) AF: 0.436 AC: 6652 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1286 AN: 3468

East Asian (EAS) AF: 0.567 AC: 2936 AN: 5178

South Asian (SAS) AF: 0.414 AC: 1997 AN: 4822

European-Finnish (FIN) AF: 0.477 AC: 5032 AN: 10560

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29393 AN: 67956

Other (OTH) AF: 0.378 AC: 796 AN: 2108

Alfa AF: 0.425 Hom.: 2339

Bravo AF: 0.412

Asia WGS AF: 0.421 AC: 1463 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.65
PhyloP100		0.75
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: rs641221; hg19: chr5-32439324;