rs12220375

Variant names:

• chr10-103141734-T-C
• rs12220375
• NM_001351169.2:c.102-2255A>G

Variant summary

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

The NM_001351169.2(NT5C2):​c.102-2255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 152,220 control chromosomes in the GnomAD database, including 848 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 0.089 (848 hom., cov: 32)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 28 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

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.102-2255A>G		intron	N/A	NP_001338098.1	P49902-1
	NT5C2	NM_001351170.2		c.102-2255A>G		intron	N/A	NP_001338099.1	A0A6Q8PHP0
	NT5C2	NM_001351171.2		c.102-2255A>G		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.102-2255A>G		intron	N/A	ENSP00000383960.3	P49902-1
	NT5C2	ENST00000343289.9	TSL:1	c.102-2255A>G		intron	N/A	ENSP00000339479.5	P49902-1
	NT5C2	ENST00000874311.1		c.102-2255A>G		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes AF: 0.0888 AC: 13514 AN: 152102 Hom.: 843 Cov.: 32

Gnomad AFR AF: 0.0397

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0889 AC: 13530 AN: 152220 Hom.: 848 Cov.: 32 AF XY: 0.0910 AC XY: 6776 AN XY: 74438

African (AFR) AF: 0.0397 AC: 1650 AN: 41544

American (AMR) AF: 0.137 AC: 2091 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1430 AN: 5162

South Asian (SAS) AF: 0.184 AC: 888 AN: 4824

European-Finnish (FIN) AF: 0.0742 AC: 785 AN: 10584

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0907 AC: 6168 AN: 68030

Other (OTH) AF: 0.105 AC: 221 AN: 2110

Alfa AF: 0.0775 Hom.: 211

Bravo AF: 0.0920

Asia WGS AF: 0.196 AC: 676 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.059
DANN	Benign	0.72
PhyloP100		-2.1
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: rs12220375; hg19: chr10-104901491;