Genetic Variant ZPR1:p.Glu237Lys (chr11-116785143-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 13/22 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

Publications

16 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3387923.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003904.5. 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
	ZPR1	NM_003904.5	MANE Select	c.709G>A	p.Glu237Lys	missense	Exon 7 of 14	NP_003895.1	O75312
	ZPR1	NM_001317086.2		c.547G>A	p.Glu183Lys	missense	Exon 6 of 13	NP_001304015.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZPR1	ENST00000227322.8	TSL:1 MANE Select	c.709G>A	p.Glu237Lys	missense	Exon 7 of 14	ENSP00000227322.3	O75312
ZPR1	ENST00000900046.1		c.739G>A	p.Glu247Lys	missense	Exon 7 of 14	ENSP00000570105.1
ZPR1	ENST00000900049.1		c.709G>A	p.Glu237Lys	missense	Exon 7 of 14	ENSP00000570108.1

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

GnomAD2 exomes

AF:

0.00437

AC:

1098

AN:

251376

AF XY:

0.00437

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 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

African (AFR)

AF:

0.000717

AC:

AN:

33476

American (AMR)

AF:

0.00391

AC:

175

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00597

AC:

156

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00110

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00171

AC:

AN:

53332

Middle Eastern (MID)

AF:

0.00700

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00587

AC:

6528

AN:

1112002

Other (OTH)

AF:

0.00480

AC:

290

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

397

793

1190

1586

1983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00408

AC:

621

AN:

152320

Hom.:

Cov.:

AF XY:

0.00376

AC XY:

280

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000794

AC:

AN:

41586

American (AMR)

AF:

0.00555

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000828

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000942

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00623

AC:

424

AN:

68022

Other (OTH)

AF:

0.0109

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00568

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

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

PhyloP100

2.8

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

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over