NM_003875.3:c.1677-418A>G

Variant names:

• chr3-155934498-A-G
• rs7651038
• NM_003875.3:c.1677-418A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003875.3(GMPS):​c.1677-418A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 152,048 control chromosomes in the GnomAD database, including 14,475 homozygotes. 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: 𝑓 0.40 (14475 hom., cov: 31)
• Consequence: GMPS NM_003875.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129
• Publications: 2 publications found

Genes affected

GMPS (HGNC:4378): (guanine monophosphate synthase) In the de novo synthesis of purine nucleotides, IMP is the branch point metabolite at which point the pathway diverges to the synthesis of either guanine or adenine nucleotides. In the guanine nucleotide pathway, there are 2 enzymes involved in converting IMP to GMP, namely IMP dehydrogenase (IMPD1), which catalyzes the oxidation of IMP to XMP, and GMP synthetase, which catalyzes the amination of XMP to GMP. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GMPS	NM_003875.3	c.1677-418A>G		intron_variant	Intron 13 of 15	ENST00000496455.7	NP_003866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GMPS	ENST00000496455.7	c.1677-418A>G		intron_variant	Intron 13 of 15	1	NM_003875.3	ENSP00000419851.1
GMPS	ENST00000295920.7	c.1380-418A>G		intron_variant	Intron 11 of 13	2		ENSP00000295920.7

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60377 AN: 151930 Hom.: 14474 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.430

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.397 AC: 60390 AN: 152048 Hom.: 14475 Cov.: 31 AF XY: 0.398 AC XY: 29560 AN XY: 74314

African (AFR) AF: 0.129 AC: 5351 AN: 41488

American (AMR) AF: 0.428 AC: 6545 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2002 AN: 3470

East Asian (EAS) AF: 0.438 AC: 2264 AN: 5164

South Asian (SAS) AF: 0.272 AC: 1313 AN: 4820

European-Finnish (FIN) AF: 0.567 AC: 5977 AN: 10550

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35440 AN: 67958

Other (OTH) AF: 0.429 AC: 907 AN: 2112

Alfa AF: 0.445 Hom.: 2069

Bravo AF: 0.382

Asia WGS AF: 0.332 AC: 1154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.9
DANN	Benign	0.87
PhyloP100		-0.13
Mutation Taster		=100/0	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: rs7651038; hg19: chr3-155652287;