Variant chr11-116779049-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003904.5(ZPR1):c.1256C>T(p.Ala419Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,614,048 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 44 hom. )

Consequence

ZPR1
NM_003904.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 9.60

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009350061).

BP6

Variant 11-116779049-G-A is Benign according to our data. Variant chr11-116779049-G-A is described in ClinVar as [Benign]. Clinvar id is 778441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00208 (317/152292) while in subpopulation AMR AF= 0.0193 (295/15302). AF 95% confidence interval is 0.0175. There are 6 homozygotes in gnomad4. There are 192 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZPR1	NM_003904.5 linkuse as main transcript	c.1256C>T	p.Ala419Val	missense_variant	14/14	ENST00000227322.8
ZPR1	NM_001317086.2 linkuse as main transcript	c.1094C>T	p.Ala365Val	missense_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZPR1	ENST00000227322.8 linkuse as main transcript	c.1256C>T	p.Ala419Val	missense_variant	14/14	1	NM_003904.5	P1
ZPR1	ENST00000444935.5 linkuse as main transcript	c.1169C>T	p.Ala390Val	missense_variant	13/13	5
ZPR1	ENST00000429220.5 linkuse as main transcript	c.1037C>T	p.Ala346Val	missense_variant	12/12	5

Frequencies

GnomAD3 genomes

AF:

0.00209

AC:

318

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0194

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00521

AC:

1310

AN:

251304

Hom.:

AF XY:

0.00357

AC XY:

485

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0370

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00114

AC:

1666

AN:

1461756

Hom.:

Cov.:

AF XY:

0.000898

AC XY:

653

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0354

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.00208

AC:

317

AN:

152292

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.0193

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.000246

Hom.:

Bravo

AF:

0.00360

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00386

AC:

469

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.44

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0094

MetaSVM

Uncertain

-0.13

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.32

Sift

Benign

0.20

Sift4G

Benign

0.073

Polyphen

1.0

Vest4

0.61

MVP

0.68

MPC

0.39

ClinPred

0.099

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over