Variant chr11-116782176-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003904.5(ZPR1):c.1161T>A(p.Phe387Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0066 in 1,614,064 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 56 hom. )

Consequence

ZPR1
NM_003904.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.344

Variant links:

Genes affected

ZPR1 (HGNC:13051): (ZPR1 zinc finger) The protein encoded by this gene is found in the cytoplasm of quiescent cells but translocates to the nucleolus in proliferating cells. The encoded protein interacts with survival motor neuron protein (SMN1) to enhance pre-mRNA splicing and to induce neuronal differentiation and axonal growth. Defects in this gene or the SMN1 gene can cause spinal muscular atrophy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

ZPR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011996299).

BP6

Variant 11-116782176-A-T is Benign according to our data. Variant chr11-116782176-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2642396.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZPR1	NM_003904.5 linkuse as main transcript	c.1161T>A	p.Phe387Leu	missense_variant	12/14	ENST00000227322.8
ZPR1	NM_001317086.2 linkuse as main transcript	c.999T>A	p.Phe333Leu	missense_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZPR1	ENST00000227322.8 linkuse as main transcript	c.1161T>A	p.Phe387Leu	missense_variant	12/14	1	NM_003904.5	P1
ZPR1	ENST00000429220.5 linkuse as main transcript	c.942T>A	p.Phe314Leu	missense_variant	10/12	5
ZPR1	ENST00000444935.5 linkuse as main transcript	c.1091+743T>A		intron_variant		5
ZPR1	ENST00000449430.1 linkuse as main transcript	c.*364T>A		3_prime_UTR_variant, NMD_transcript_variant	8/8	3

Frequencies

GnomAD3 genomes

AF:

0.00520

AC:

791

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00425

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00998

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00772

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00495

AC:

1243

AN:

251340

Hom.:

AF XY:

0.00470

AC XY:

638

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00823

Gnomad NFE exome

AF:

0.00785

Gnomad OTH exome

AF:

0.00571

GnomAD4 exome

AF:

0.00674

AC:

9857

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

4695

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.00809

Gnomad4 NFE exome

AF:

0.00797

Gnomad4 OTH exome

AF:

0.00576

GnomAD4 genome

AF:

0.00519

AC:

791

AN:

152312

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

377

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00998

Gnomad4 NFE

AF:

0.00772

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.00697

Hom.:

Bravo

AF:

0.00500

TwinsUK

AF:

0.0105

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00803

AC:

ExAC

AF:

0.00488

AC:

592

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00715

EpiControl

AF:

0.00557

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

ZPR1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Benign

0.016

Eigen_PC

Benign

0.0023

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.81

M_CAP

Benign

0.046

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.28

Sift

Benign

0.042

Sift4G

Uncertain

0.055

Polyphen

0.97

Vest4

0.73

MutPred

0.78

Gain of disorder (P = 0.1458);

MVP

0.48

MPC

1.1

ClinPred

0.057

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.59

gMVP

0.73

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over