Variant 6-16246950-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006877.4(GMPR):c.196G>A(p.Val66Met) variant causes a missense change. The variant allele was found at a frequency of 0.000523 in 1,613,916 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 1 hom. )

Consequence

GMPR
NM_006877.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.40

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019683361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMPR	NM_006877.4 link	c.196G>A	p.Val66Met	missense_variant	Exon 2 of 9	ENST00000259727.5	NP_006868.3	P36959
GMPR	XM_047418656.1 link	c.196G>A	p.Val66Met	missense_variant	Exon 2 of 9		XP_047274612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMPR	ENST00000259727.5 link	c.196G>A	p.Val66Met	missense_variant	Exon 2 of 9	1	NM_006877.4	ENSP00000259727.4		P36959

Frequencies

GnomAD3 genomes

AF:

0.000480

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000462

AC:

116

AN:

251284

Hom.:

AF XY:

0.000427

AC XY:

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00466

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000484

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000527

AC:

771

AN:

1461652

Hom.:

Cov.:

AF XY:

0.000517

AC XY:

376

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00486

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000513

Gnomad4 OTH exome

AF:

0.000894

GnomAD4 genome

AF:

0.000479

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000641

Hom.:

Bravo

AF:

0.000412

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000428

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000533

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.196G>A (p.V66M) alteration is located in exon 2 (coding exon 2) of the GMPR gene. This alteration results from a G to A substitution at nucleotide position 196, causing the valine (V) at amino acid position 66 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.033

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.7

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.46

Sift

Benign

0.055

Sift4G

Benign

0.16

Polyphen

0.91

Vest4

0.23

MVP

0.83

MPC

0.24

ClinPred

0.065

GERP RS

4.5

Varity_R

0.25

gMVP

0.77

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