rs554383030

Variant names:

• chr6-16238710-C-G
• rs554383030
• NM_006877.4:c.17C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-16238710-C-G
• chr6-16238710-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006877.4(GMPR):​c.17C>G​(p.Ala6Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000782 in 1,279,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A6V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: GMPR NM_006877.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.65
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.098205715).

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.17C>G	p.Ala6Gly	missense	Exon 1 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.17C>G	p.Ala6Gly	missense	Exon 1 of 9	ENSP00000259727.4	P36959
	GMPR	ENST00000864761.1		c.17C>G	p.Ala6Gly	missense	Exon 1 of 10	ENSP00000534820.1
	GMPR	ENST00000967431.1		c.17C>G	p.Ala6Gly	missense	Exon 1 of 10	ENSP00000637490.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000968 AC: 1 AN: 103294 AF XY: 0.0000177

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000614

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.82e-7 AC: 1 AN: 1279032 Hom.: 0 Cov.: 28 AF XY: 0.00000159 AC XY: 1 AN XY: 629616

African (AFR) AF: 0.00 AC: 0 AN: 26786

American (AMR) AF: 0.0000370 AC: 1 AN: 27026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22052

East Asian (EAS) AF: 0.00 AC: 0 AN: 28194

South Asian (SAS) AF: 0.00 AC: 0 AN: 63978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4402

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1010906

Other (OTH) AF: 0.00 AC: 0 AN: 51272

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.20
Sift	Benign	0.13	T
Sift4G	Benign	0.33	T
Polyphen		0.0070	B
Vest4		0.25
MutPred		0.19		Loss of loop (P = 0.0986)
MVP		0.73
MPC		0.078
ClinPred		0.36	T
GERP RS		2.3
PromoterAI		0.088	Neutral
Varity_R		0.20
gMVP		0.47
Mutation Taster		=40/60	disease causing

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: rs554383030; hg19: chr6-16238941;