chr6-16290530-T-A

Variant names:

• chr6-16290530-T-A
• rs1042391
• NM_006877.4:c.766T>A

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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
• Publications: 44 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006877.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMPR	NM_006877.4	MANE Select	c.766T>A	p.Phe256Ile	missense	Exon 8 of 9	NP_006868.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMPR	ENST00000259727.5	TSL:1 MANE Select	c.766T>A	p.Phe256Ile	missense	Exon 8 of 9	ENSP00000259727.4	P36959
	GMPR	ENST00000864761.1		c.961T>A	p.Phe321Ile	missense	Exon 9 of 10	ENSP00000534820.1
	GMPR	ENST00000967431.1		c.859T>A	p.Phe287Ile	missense	Exon 9 of 10	ENSP00000637490.1

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

GnomAD2 exomes AF: 0.536 AC: 134870 AN: 251488 AF XY: 0.528

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 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

African (AFR) AF: 0.846 AC: 28321 AN: 33470

American (AMR) AF: 0.581 AC: 25960 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 12841 AN: 26134

East Asian (EAS) AF: 0.881 AC: 34966 AN: 39694

South Asian (SAS) AF: 0.649 AC: 55963 AN: 86232

European-Finnish (FIN) AF: 0.505 AC: 26965 AN: 53416

Middle Eastern (MID) AF: 0.407 AC: 2344 AN: 5766

European-Non Finnish (NFE) AF: 0.388 AC: 431164 AN: 1111298

Other (OTH) AF: 0.477 AC: 28801 AN: 60366

GnomAD4 genome AF: 0.565 AC: 85805 AN: 151996 Hom.: 27210 Cov.: 31 AF XY: 0.572 AC XY: 42503 AN XY: 74282

African (AFR) AF: 0.831 AC: 34458 AN: 41484

American (AMR) AF: 0.544 AC: 8306 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1695 AN: 3466

East Asian (EAS) AF: 0.881 AC: 4552 AN: 5164

South Asian (SAS) AF: 0.671 AC: 3226 AN: 4808

European-Finnish (FIN) AF: 0.497 AC: 5250 AN: 10562

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26898 AN: 67942

Other (OTH) AF: 0.509 AC: 1072 AN: 2108

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	GMPR POLYMORPHISM (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		4.3
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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