Genetic Variant ZPR1:c.981+87T>C (chr11-116783443-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003904.5(ZPR1):c.981+87T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,191,872 control chromosomes in the GnomAD database, including 31,695 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 0.19 ( 3358 hom., cov: 32)

Exomes 𝑓: 0.22 ( 28337 hom. )

Consequence

ZPR1
NM_003904.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.633

Publications

21 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZPR1	NM_003904.5 link	c.981+87T>C		intron_variant	Intron 10 of 13	ENST00000227322.8	NP_003895.1	O75312
ZPR1	NM_001317086.2 link	c.819+87T>C		intron_variant	Intron 9 of 12		NP_001304015.1	O75312

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZPR1	ENST00000227322.8 link	c.981+87T>C	intron_variant	Intron 10 of 13	1	NM_003904.5	ENSP00000227322.3	O75312
ZPR1	ENST00000444935.5 link	c.978+87T>C	intron_variant	Intron 10 of 12	5		ENSP00000390391.1	H7BZM7
ZPR1	ENST00000429220.5 link	c.759+87T>C	intron_variant	Intron 8 of 11	5		ENSP00000394495.1	H7C0E5
ZPR1	ENST00000449430.1 link	n.*184+87T>C	intron_variant	Intron 6 of 7	3		ENSP00000415505.1	H7C449

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29600

AN:

151976

Hom.:

3352

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.267

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.00366

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.206

GnomAD4 exome

AF:

0.224

AC:

232781

AN:

1039778

Hom.:

28337

AF XY:

0.224

AC XY:

119314

AN XY:

532980

show subpopulations

African (AFR)

AF:

0.117

AC:

2926

AN:

25086

American (AMR)

AF:

0.136

AC:

5599

AN:

41312

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

5705

AN:

21880

East Asian (EAS)

AF:

0.000901

AC:

AN:

37746

South Asian (SAS)

AF:

0.147

AC:

10892

AN:

74240

European-Finnish (FIN)

AF:

0.236

AC:

12311

AN:

52138

Middle Eastern (MID)

AF:

0.244

AC:

1198

AN:

4902

European-Non Finnish (NFE)

AF:

0.250

AC:

184104

AN:

736254

Other (OTH)

AF:

0.217

AC:

10012

AN:

46220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

8718

17437

26155

34874

43592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4908

9816

14724

19632

24540

<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:

0.195

AC:

29628

AN:

152094

Hom.:

3358

Cov.:

AF XY:

0.192

AC XY:

14281

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.119

AC:

4925

AN:

41480

American (AMR)

AF:

0.172

AC:

2632

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

876

AN:

3472

East Asian (EAS)

AF:

0.00366

AC:

AN:

5186

South Asian (SAS)

AF:

0.132

AC:

637

AN:

4820

European-Finnish (FIN)

AF:

0.236

AC:

2498

AN:

10568

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17306

AN:

67978

Other (OTH)

AF:

0.204

AC:

429

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1217

2434

3652

4869

6086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<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:

0.228

Hom.:

2335

Bravo

AF:

0.184

Asia WGS

AF:

0.0720

AC:

250

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.4

(source)

DANN

Benign

0.70

PhyloP100

0.63

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over