3-155893564-A-T

Variant names:

• chr3-155893564-A-T
• rs1754524945
• NM_003875.3:c.74A>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003875.3(GMPS):​c.74A>T​(p.Glu25Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,624 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: GMPS NM_003875.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.10
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003875.3. 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
	GMPS	NM_003875.3	MANE Select	c.74A>T	p.Glu25Val	missense	Exon 2 of 16	NP_003866.1	A0A140VJK6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GMPS	ENST00000496455.7	TSL:1 MANE Select	c.74A>T	p.Glu25Val	missense	Exon 2 of 16	ENSP00000419851.1	P49915-1
	GMPS	ENST00000928984.1		c.74A>T	p.Glu25Val	missense	Exon 2 of 16	ENSP00000599043.1
	GMPS	ENST00000967990.1		c.74A>T	p.Glu25Val	missense	Exon 2 of 16	ENSP00000638049.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1460624 Hom.: 0 Cov.: 29 AF XY: 0.00000826 AC XY: 6 AN XY: 726632

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111012

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0099	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.2	L
PhyloP100		9.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.39
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.16	T
Polyphen		0.011	B
Vest4		0.71
MutPred		0.55		Loss of disorder (P = 0.0492)
MVP		0.76
MPC		0.44
ClinPred		0.81	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.28
gMVP		0.67
Mutation Taster		=30/70	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1754524945; hg19: chr3-155611353;