Genetic Variant NM_003904.5:c.*506C>T (chr11-116778419-G-A) – 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.*506C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,688 control chromosomes in the GnomAD database, including 1,121 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 0.11 ( 1121 hom., cov: 32)

Exomes 𝑓: 0.021 ( 0 hom. )

Consequence

ZPR1
NM_003904.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.265

Publications

27 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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPR1	NM_003904.5	MANE Select	c.*506C>T		3_prime_UTR	Exon 14 of 14	NP_003895.1
	ZPR1	NM_001317086.2		c.*506C>T		3_prime_UTR	Exon 13 of 13	NP_001304015.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZPR1	ENST00000227322.8	TSL:1 MANE Select	c.*506C>T	3_prime_UTR	Exon 14 of 14	ENSP00000227322.3
ZPR1	ENST00000444935.5	TSL:5	c.*506C>T	3_prime_UTR	Exon 13 of 13	ENSP00000390391.1
ZPR1	ENST00000429220.5	TSL:5	c.*506C>T	3_prime_UTR	Exon 12 of 12	ENSP00000394495.1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16076

AN:

152104

Hom.:

1118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.0858

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0429

Gnomad FIN

AF:

0.0537

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0670

Gnomad OTH

AF:

0.111

GnomAD4 exome

AF:

0.0215

AC:

AN:

466

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

AN XY:

244

show subpopulations

African (AFR)

AF:

0.167

AC:

AN:

American (AMR)

AF:

0.0400

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.100

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0152

AC:

AN:

328

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.106

AC:

16113

AN:

152222

Hom.:

1121

Cov.:

AF XY:

0.105

AC XY:

7781

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.193

AC:

8031

AN:

41520

American (AMR)

AF:

0.135

AC:

2059

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0858

AC:

298

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0431

AC:

208

AN:

4822

European-Finnish (FIN)

AF:

0.0537

AC:

570

AN:

10608

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0670

AC:

4559

AN:

68002

Other (OTH)

AF:

0.110

AC:

233

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

734

1468

2202

2936

3670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0784

Hom.:

1890

Bravo

AF:

0.116

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.1

(source)

DANN

Benign

0.67

PhyloP100

-0.27

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over