Genetic Variant NM_003904.5:c.*724C>G (chr11-116778201-G-C) – 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.*724C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 152,238 control chromosomes in the GnomAD database, including 51,799 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 0.82 ( 51773 hom., cov: 32)

Exomes 𝑓: 0.88 ( 26 hom. )

Consequence

ZPR1
NM_003904.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.346

Publications

508 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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZPR1	NM_003904.5 link	c.*724C>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000227322.8	NP_003895.1
ZPR1	NM_001317086.2 link	c.*724C>G		3_prime_UTR_variant	Exon 13 of 13		NP_001304015.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
ZPR1	ENST00000227322.8 link	c.*724C>G	3_prime_UTR_variant	Exon 14 of 14	1	NM_003904.5	ENSP00000227322.3
ZPR1	ENST00000444935.5 link	c.*724C>G	3_prime_UTR_variant	Exon 13 of 13	5		ENSP00000390391.1
ZPR1	ENST00000429220.5 link	c.*724C>G	3_prime_UTR_variant	Exon 12 of 12	5		ENSP00000394495.1

Frequencies

GnomAD3 genomes

AF:

0.823

AC:

125152

AN:

152052

Hom.:

51754

Cov.:

show subpopulations

Gnomad AFR

AF:

0.791

Gnomad AMI

AF:

0.773

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.824

Gnomad EAS

AF:

0.768

Gnomad SAS

AF:

0.766

Gnomad FIN

AF:

0.863

Gnomad MID

AF:

0.756

Gnomad NFE

AF:

0.862

Gnomad OTH

AF:

0.808

GnomAD4 exome

AF:

0.882

AC:

AN:

Hom.:

Cov.:

AF XY:

0.909

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.833

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.870

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.588

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.823

AC:

125222

AN:

152170

Hom.:

51773

Cov.:

AF XY:

0.821

AC XY:

61051

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.791

AC:

32809

AN:

41484

American (AMR)

AF:

0.752

AC:

11499

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.824

AC:

2856

AN:

3466

East Asian (EAS)

AF:

0.767

AC:

3974

AN:

5182

South Asian (SAS)

AF:

0.765

AC:

3691

AN:

4822

European-Finnish (FIN)

AF:

0.863

AC:

9146

AN:

10596

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.862

AC:

58623

AN:

68008

Other (OTH)

AF:

0.804

AC:

1697

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1141

2282

3422

4563

5704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<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:

0.852

Hom.:

30562

Bravo

AF:

0.813

Asia WGS

AF:

0.765

AC:

2662

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.48

(source)

DANN

Benign

0.42

PhyloP100

-0.35

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