rs66473231

Variant names:

• chr10-103092903-A-AAACTT
• rs66473231
• NM_001351169.2:c.1159+235_1159+236insAAGTT

Variant summary

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

The NM_001351169.2(NT5C2):​c.1159+235_1159+236insAAGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 0 publications found

Genes affected

NT5C2 (HGNC:8022): (5'-nucleotidase, cytosolic II) This gene encodes a hydrolase that serves as an important role in cellular purine metabolism by acting primarily on inosine 5'-monophosphate and other purine nucleotides. [provided by RefSeq, Oct 2011]

NT5C2 Gene-Disease associations (from GenCC):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 45

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351169.2. 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
	NT5C2	NM_001351169.2	MANE Select	c.1159+235_1159+236insAAGTT		intron	N/A	NP_001338098.1	P49902-1
	NT5C2	NM_001351170.2		c.1183+235_1183+236insAAGTT		intron	N/A	NP_001338099.1	A0A6Q8PHP0
	NT5C2	NM_001351171.2		c.1183+235_1183+236insAAGTT		intron	N/A	NP_001338100.1	A0A6Q8PHP0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	ENST00000404739.8	TSL:1 MANE Select	c.1159+235_1159+236insAAGTT		intron	N/A	ENSP00000383960.3	P49902-1
	NT5C2	ENST00000343289.9	TSL:1	c.1159+235_1159+236insAAGTT		intron	N/A	ENSP00000339479.5	P49902-1
	NT5C2	ENST00000874311.1		c.1375+235_1375+236insAAGTT		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.20

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs66473231; hg19: chr10-104852660;