6-16250323-G-C

Variant names:

• chr6-16250323-G-C
• rs747349583
• NM_006877.4:c.247G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006877.4(GMPR):​c.247G>C​(p.Asp83His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: GMPR NM_006877.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.46

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4006067).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMPR	NM_006877.4	c.247G>C	p.Asp83His	missense_variant	Exon 3 of 9	ENST00000259727.5	NP_006868.3
GMPR	XM_047418656.1	c.247G>C	p.Asp83His	missense_variant	Exon 3 of 9		XP_047274612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMPR	ENST00000259727.5	c.247G>C	p.Asp83His	missense_variant	Exon 3 of 9	1	NM_006877.4	ENSP00000259727.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251356 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135860

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458898 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 726020

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.87	D
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.022	D
Polyphen		0.019	B
Vest4		0.35
MutPred		0.46		Loss of helix (P = 0.0104);
MVP		0.92
MPC		0.10
ClinPred		0.78	D
GERP RS		6.1
Varity_R		0.57
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs747349583; hg19: chr6-16250554;