rs187670203

Variant names:

• chr3-155914549-C-A
• rs187670203
• NM_003875.3:c.1017C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-155914549-C-A
• chr3-155914549-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003875.3(GMPS):​c.1017C>A​(p.Ile339Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,430,200 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. Synonymous variant affecting the same amino acid position (i.e. I339I) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GMPS NM_003875.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.100
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BP7: Synonymous conserved (PhyloP=0.1 with no splicing effect.

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.1017C>A	p.Ile339Ile	synonymous	Exon 8 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.1017C>A	p.Ile339Ile	synonymous	Exon 8 of 16	ENSP00000419851.1	P49915-1
	GMPS	ENST00000928984.1		c.1017C>A	p.Ile339Ile	synonymous	Exon 8 of 16	ENSP00000599043.1
	GMPS	ENST00000967990.1		c.1017C>A	p.Ile339Ile	synonymous	Exon 8 of 16	ENSP00000638049.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1430200 Hom.: 0 Cov.: 28 AF XY: 0.00000281 AC XY: 2 AN XY: 710760

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31614

American (AMR) AF: 0.0000264 AC: 1 AN: 37878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25104

East Asian (EAS) AF: 0.00 AC: 0 AN: 38204

South Asian (SAS) AF: 0.00 AC: 0 AN: 79284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 9.09e-7 AC: 1 AN: 1100304

Other (OTH) AF: 0.00 AC: 0 AN: 59096

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	7.9
DANN	Benign	0.74
PhyloP100		0.10

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: rs187670203; hg19: chr3-155632338;