rs1042391

chr6-16290530-T-Achr6-16290530-T-Cchr6-16290530-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. 12/19 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
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 4.30

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]

ACMG classification

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	UniProt
GMPR	NM_006877.4	c.766T>A	p.Phe256Ile	missense_variant	8/9	ENST00000259727.5
GMPR	XM_047418656.1	c.909T>A	p.Cys303Ter	stop_gained	9/9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85684 AN: 151878 Hom.: 27151 Cov.: 31

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

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.: 36 AF XY: 0.447 AC XY: 325040 AN XY: 726886

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.: 31 AF XY: 0.572 AC XY: 42503 AN XY: 74282

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

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	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	17
Dann	Benign	0.52
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	6.7e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.3	N
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	3.7	N
REVEL	Benign	0.24
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.087
MPC		0.11
ClinPred		0.0055	T
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

Other links and lift over

dbSNP: rs1042391; hg19: chr6-16290761; COSMIC: COSV52475081;