chr10-103138228-T-C

Variant names:

• chr10-103138228-T-C
• rs11598702
• NM_001351169.2:c.175+1178A>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.175+1178A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 152,048 control chromosomes in the GnomAD database, including 7,373 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 0.30 (7373 hom., cov: 32)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 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.175+1178A>G		intron	N/A	NP_001338098.1	P49902-1
	NT5C2	NM_001351170.2		c.175+1178A>G		intron	N/A	NP_001338099.1	A0A6Q8PHP0
	NT5C2	NM_001351171.2		c.175+1178A>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.175+1178A>G		intron	N/A	ENSP00000383960.3	P49902-1
	NT5C2	ENST00000343289.9	TSL:1	c.175+1178A>G		intron	N/A	ENSP00000339479.5	P49902-1
	NT5C2	ENST00000874311.1		c.176-922A>G		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46155 AN: 151930 Hom.: 7372 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.304 AC: 46159 AN: 152048 Hom.: 7373 Cov.: 32 AF XY: 0.300 AC XY: 22262 AN XY: 74316

African (AFR) AF: 0.202 AC: 8386 AN: 41478

American (AMR) AF: 0.301 AC: 4603 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1329 AN: 3464

East Asian (EAS) AF: 0.239 AC: 1238 AN: 5174

South Asian (SAS) AF: 0.262 AC: 1260 AN: 4818

European-Finnish (FIN) AF: 0.289 AC: 3049 AN: 10560

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25106 AN: 67968

Other (OTH) AF: 0.310 AC: 655 AN: 2110

Alfa AF: 0.349 Hom.: 41437

Bravo AF: 0.299

Asia WGS AF: 0.245 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.6
DANN	Benign	0.58
PhyloP100		0.31
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: rs11598702; hg19: chr10-104897985;