Variant rs1042391 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006877.4(GMPR):c.766T>A(p.Phe256Ile) variant causes a missense change. The variant allele was found at a frequency of 0.454 in 1,613,092 control chromosomes in the GnomAD database, including 182,578 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.56 ( 27210 hom., cov: 31)

Exomes 𝑓: 0.44 ( 155368 hom. )

Consequence

GMPR
NM_006877.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.30

Variant links:

Genes affected

GMPR (HGNC:4376): (guanosine monophosphate reductase) This gene encodes an enzyme that catalyzes the irreversible and NADPH-dependent reductive deamination of GMP to IMP. The protein also functions in the re-utilization of free intracellular bases and purine nucleosides.[provided by RefSeq, Oct 2009]

GMPR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.7436486E-7).

BP6

Variant 6-16290530-T-A is Benign according to our data. Variant chr6-16290530-T-A is described in ClinVar as [Benign]. Clinvar id is 15961.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMPR	NM_006877.4 linkuse as main transcript	c.766T>A	p.Phe256Ile	missense_variant	8/9	ENST00000259727.5	NP_006868.3
GMPR	XM_047418656.1 linkuse as main transcript	c.909T>A	p.Cys303Ter	stop_gained	9/9		XP_047274612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GMPR	ENST00000259727.5 linkuse as main transcript	c.766T>A	p.Phe256Ile	missense_variant	8/9	1	NM_006877.4	ENSP00000259727	P1
GMPR	ENST00000540478.1 linkuse as main transcript	n.586T>A		non_coding_transcript_exon_variant	1/2	2
GMPR	ENST00000543191.5 linkuse as main transcript	n.261T>A		non_coding_transcript_exon_variant	3/4	2
GMPR	ENST00000544145.1 linkuse as main transcript	n.120T>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.564

AC:

85684

AN:

151878

Hom.:

27151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.831

Gnomad AMI

AF:

0.253

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.882

Gnomad SAS

AF:

0.672

Gnomad FIN

AF:

0.497

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.501

GnomAD3 exomes

AF:

0.536

AC:

134870

AN:

251488

Hom.:

39611

AF XY:

0.528

AC XY:

71737

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.839

Gnomad AMR exome

AF:

0.584

Gnomad ASJ exome

AF:

0.494

Gnomad EAS exome

AF:

0.886

Gnomad SAS exome

AF:

0.655

Gnomad FIN exome

AF:

0.504

Gnomad NFE exome

AF:

0.403

Gnomad OTH exome

AF:

0.478

GnomAD4 exome

AF:

0.443

AC:

647325

AN:

1461096

Hom.:

155368

Cov.:

AF XY:

0.447

AC XY:

325040

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.846

Gnomad4 AMR exome

AF:

0.581

Gnomad4 ASJ exome

AF:

0.491

Gnomad4 EAS exome

AF:

0.881

Gnomad4 SAS exome

AF:

0.649

Gnomad4 FIN exome

AF:

0.505

Gnomad4 NFE exome

AF:

0.388

Gnomad4 OTH exome

AF:

0.477

GnomAD4 genome

AF:

0.565

AC:

85805

AN:

151996

Hom.:

27210

Cov.:

AF XY:

0.572

AC XY:

42503

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.831

Gnomad4 AMR

AF:

0.544

Gnomad4 ASJ

AF:

0.489

Gnomad4 EAS

AF:

0.881

Gnomad4 SAS

AF:

0.671

Gnomad4 FIN

AF:

0.497

Gnomad4 NFE

AF:

0.396

Gnomad4 OTH

AF:

0.509

Alfa

AF:

0.438

Hom.:

12163

Bravo

AF:

0.578

TwinsUK

AF:

0.376

AC:

1395

ALSPAC

AF:

0.388

AC:

1497

ESP6500AA

AF:

0.822

AC:

3623

ESP6500EA

AF:

0.391

AC:

3366

ExAC

AF:

0.544

AC:

66091

Asia WGS

AF:

0.800

AC:

2781

AN:

3478

EpiCase

AF:

0.387

EpiControl

AF:

0.389

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

GMP REDUCTASE POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Nov 04, 2020

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 13, 2018

This variant is associated with the following publications: (PMID: 29874175) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.52

DEOGEN2

Benign

0.38

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.41

MetaRNN

Benign

6.7e-7

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-2.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

3.7

REVEL

Benign

0.24

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.087

MPC

0.11

ClinPred

0.0055

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.050

gMVP

0.67

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