Genetic Variant NM_003904.5:c.333+167A>C (chr11-116787315-T-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.333+167A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 740,678 control chromosomes in the GnomAD database, including 2,338 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 0.096 ( 894 hom., cov: 33)

Exomes 𝑓: 0.064 ( 1444 hom. )

Consequence

ZPR1
NM_003904.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.826

Publications

17 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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ZPR1	NM_003904.5 link	c.333+167A>C	intron_variant	Intron 2 of 13	ENST00000227322.8	NP_003895.1	O75312
ZPR1	NM_001317086.2 link	c.172-256A>C	intron_variant	Intron 1 of 12		NP_001304015.1	O75312
ZPR1	XM_047427804.1 link	c.333+167A>C	intron_variant	Intron 2 of 8		XP_047283760.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZPR1	ENST00000227322.8 link	c.333+167A>C		intron_variant	Intron 2 of 13	1	NM_003904.5	ENSP00000227322.3		O75312

Frequencies

GnomAD3 genomes

AF:

0.0956

AC:

14539

AN:

152142

Hom.:

889

Cov.:

show subpopulations

Gnomad AFR

AF:

0.164

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.0740

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0449

Gnomad FIN

AF:

0.0539

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0645

Gnomad OTH

AF:

0.103

GnomAD4 exome

AF:

0.0636

AC:

37426

AN:

588418

Hom.:

1444

Cov.:

AF XY:

0.0622

AC XY:

18860

AN XY:

303222

show subpopulations

African (AFR)

AF:

0.158

AC:

2342

AN:

14818

American (AMR)

AF:

0.141

AC:

2678

AN:

18982

Ashkenazi Jewish (ASJ)

AF:

0.0689

AC:

1004

AN:

14570

East Asian (EAS)

AF:

0.000723

AC:

AN:

31832

South Asian (SAS)

AF:

0.0432

AC:

2094

AN:

48510

European-Finnish (FIN)

AF:

0.0617

AC:

2126

AN:

34458

Middle Eastern (MID)

AF:

0.0869

AC:

326

AN:

3752

European-Non Finnish (NFE)

AF:

0.0629

AC:

24586

AN:

390826

Other (OTH)

AF:

0.0733

AC:

2247

AN:

30670

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1797

3594

5392

7189

8986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.0957

AC:

14575

AN:

152260

Hom.:

894

Cov.:

AF XY:

0.0946

AC XY:

7043

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.165

AC:

6835

AN:

41524

American (AMR)

AF:

0.127

AC:

1937

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0740

AC:

257

AN:

3472

East Asian (EAS)

AF:

0.000771

AC:

AN:

5186

South Asian (SAS)

AF:

0.0452

AC:

218

AN:

4824

European-Finnish (FIN)

AF:

0.0539

AC:

572

AN:

10620

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0645

AC:

4389

AN:

68012

Other (OTH)

AF:

0.102

AC:

216

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

654

1308

1961

2615

3269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<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:

0.0840

Hom.:

158

Bravo

AF:

0.105

Asia WGS

AF:

0.0400

AC:

139

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.7

(source)

DANN

Benign

0.68

PhyloP100

-0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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