rs11191561

Variant names:

• chr10-103109774-C-G
• rs11191561
• NM_001351169.2:c.176-3068G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-103109774-C-G
• chr10-103109774-C-T

Variant summary

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

The NM_001351169.2(NT5C2):​c.176-3068G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,124 control chromosomes in the GnomAD database, including 1,364 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 0.13 (1364 hom., cov: 32)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.565
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.142 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.176-3068G>C		intron	N/A	NP_001338098.1	P49902-1
	NT5C2	NM_001351170.2		c.176-3068G>C		intron	N/A	NP_001338099.1	A0A6Q8PHP0
	NT5C2	NM_001351171.2		c.176-3068G>C		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.176-3068G>C		intron	N/A	ENSP00000383960.3	P49902-1
	NT5C2	ENST00000343289.9	TSL:1	c.176-3068G>C		intron	N/A	ENSP00000339479.5	P49902-1
	NT5C2	ENST00000874311.1		c.367+1971G>C		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20093 AN: 152006 Hom.: 1365 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.132 AC: 20095 AN: 152124 Hom.: 1364 Cov.: 32 AF XY: 0.129 AC XY: 9573 AN XY: 74356

African (AFR) AF: 0.118 AC: 4890 AN: 41494

American (AMR) AF: 0.126 AC: 1921 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3470

East Asian (EAS) AF: 0.150 AC: 778 AN: 5176

South Asian (SAS) AF: 0.151 AC: 727 AN: 4808

European-Finnish (FIN) AF: 0.0652 AC: 690 AN: 10586

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9737 AN: 68006

Other (OTH) AF: 0.163 AC: 343 AN: 2106

Alfa AF: 0.126 Hom.: 169

Bravo AF: 0.137

Asia WGS AF: 0.145 AC: 506 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.0
DANN	Benign	0.49
PhyloP100		-0.56
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: rs11191561; hg19: chr10-104869531;