Variant 11-116785143-C-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.709G>A(p.Glu237Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,614,044 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 23 hom. )

Consequence

ZPR1
NM_003904.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.76

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=0.004121095).

BP6

Variant 11-116785143-C-T is Benign according to our data. Variant chr11-116785143-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3387923.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPR1	NM_003904.5 link	c.709G>A	p.Glu237Lys	missense_variant	7/14	ENST00000227322.8	NP_003895.1	O75312
ZPR1	NM_001317086.2 link	c.547G>A	p.Glu183Lys	missense_variant	6/13		NP_001304015.1	O75312
ZPR1	XM_047427804.1 link	c.709G>A	p.Glu237Lys	missense_variant	7/9		XP_047283760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZPR1	ENST00000227322.8 link	c.709G>A	p.Glu237Lys	missense_variant	7/14	1	NM_003904.5	ENSP00000227322.3	O75312
ZPR1	ENST00000444935.5 link	c.706G>A	p.Glu236Lys	missense_variant	7/13	5		ENSP00000390391.1	H7BZM7
ZPR1	ENST00000429220.5 link	c.532-222G>A		intron_variant		5		ENSP00000394495.1	H7C0E5
ZPR1	ENST00000449430.1 link	n.175G>A		non_coding_transcript_exon_variant	3/8	3		ENSP00000415505.1	H7C449

Frequencies

GnomAD3 genomes

AF:

0.00409

AC:

622

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.0297

Gnomad AMR

AF:

0.00556

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00625

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00437

AC:

1098

AN:

251376

Hom.:

AF XY:

0.00437

AC XY:

594

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.00605

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.00157

Gnomad NFE exome

AF:

0.00704

Gnomad OTH exome

AF:

0.00538

GnomAD4 exome

AF:

0.00506

AC:

7399

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00496

AC XY:

3605

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00391

Gnomad4 ASJ exome

AF:

0.00597

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00110

Gnomad4 FIN exome

AF:

0.00171

Gnomad4 NFE exome

AF:

0.00587

Gnomad4 OTH exome

AF:

0.00480

GnomAD4 genome

AF:

0.00408

AC:

621

AN:

152320

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

280

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00555

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.000942

Gnomad4 NFE

AF:

0.00623

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00592

Hom.:

Bravo

AF:

0.00471

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00722

AC:

ExAC

AF:

0.00451

AC:

548

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00703

EpiControl

AF:

0.00865

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

Oct 01, 2024

ZPR1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Benign

0.032

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0075

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.9

REVEL

Benign

0.073

Sift

Benign

0.069

Sift4G

Benign

0.076

Polyphen

0.31

Vest4

0.21

MVP

0.72

MPC

0.36

ClinPred

0.029

GERP RS

4.8

Varity_R

0.059

gMVP

0.34

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