rs1321372503

Variant names:

• chr1-92301481-C-G
• rs1321372503
• NM_024813.3:c.125C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-92301481-C-G
• chr1-92301481-C-T

Variant summary

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

The NM_024813.3(RPAP2):​c.125C>G​(p.Ala42Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. A42V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPAP2 NM_024813.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 0 publications found

Genes affected

RPAP2 (HGNC:25791): (RNA polymerase II associated protein 2) Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in dephosphorylation of RNA polymerase II C-terminal domain and snRNA transcription. Located in cytosol and nucleolus. Part of RNA polymerase II, holoenzyme. [provided by Alliance of Genome Resources, Apr 2022]

GLMN (HGNC:14373): (glomulin, FKBP associated protein) This gene encodes a phosphorylated protein that is a member of a Skp1-Cullin-F-box-like complex. The protein is essential for normal development of the vasculature and mutations in this gene have been associated with glomuvenous malformations, also called glomangiomas. Multiple splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

GLMN Gene-Disease associations (from GenCC):

• glomuvenous malformation

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

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=0.20784289).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024813.3. 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
	RPAP2	NM_024813.3	MANE Select	c.125C>G	p.Ala42Gly	missense	Exon 3 of 13	NP_079089.2	Q8IXW5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPAP2	ENST00000610020.2	TSL:1 MANE Select	c.125C>G	p.Ala42Gly	missense	Exon 3 of 13	ENSP00000476948.1	Q8IXW5-1
	RPAP2	ENST00000957713.1		c.125C>G	p.Ala42Gly	missense	Exon 3 of 14	ENSP00000627772.1
	RPAP2	ENST00000957711.1		c.125C>G	p.Ala42Gly	missense	Exon 3 of 14	ENSP00000627770.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.42
PrimateAI	Benign	0.33	T
Sift4G	Benign	0.077	T
Polyphen		0.91	P
Vest4		0.18
MutPred		0.19		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.79
MPC		0.075
ClinPred		0.57	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1321372503; hg19: chr1-92767038;