rs11191580

Variant names:

• chr10-103146454-T-C
• rs11191580
• NM_001351169.2:c.102-6975A>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.102-6975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 984,390 control chromosomes in the GnomAD database, including 3,899 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 0.083 (819 hom., cov: 32)
  • Exomes 𝑓: 0.080 (3080 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558
• Publications: 121 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):

• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.102-6975A>G		intron_variant	Intron 3 of 18	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.102-6975A>G		intron_variant	Intron 3 of 18	1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12700 AN: 152156 Hom.: 815 Cov.: 32

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0903

Gnomad OTH AF: 0.0975

GnomAD4 exome AF: 0.0797 AC: 66304 AN: 832116 Hom.: 3080 Cov.: 26 AF XY: 0.0800 AC XY: 30739 AN XY: 384294

African (AFR) AF: 0.0107 AC: 169 AN: 15782

American (AMR) AF: 0.179 AC: 176 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.0747 AC: 384 AN: 5138

East Asian (EAS) AF: 0.275 AC: 997 AN: 3622

South Asian (SAS) AF: 0.208 AC: 3414 AN: 16396

European-Finnish (FIN) AF: 0.0833 AC: 23 AN: 276

Middle Eastern (MID) AF: 0.0846 AC: 137 AN: 1620

European-Non Finnish (NFE) AF: 0.0767 AC: 58366 AN: 761052

Other (OTH) AF: 0.0968 AC: 2638 AN: 27246

GnomAD4 genome AF: 0.0835 AC: 12709 AN: 152274 Hom.: 819 Cov.: 32 AF XY: 0.0861 AC XY: 6408 AN XY: 74458

African (AFR) AF: 0.0212 AC: 883 AN: 41556

American (AMR) AF: 0.135 AC: 2068 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0720 AC: 250 AN: 3472

East Asian (EAS) AF: 0.277 AC: 1436 AN: 5184

South Asian (SAS) AF: 0.184 AC: 886 AN: 4822

European-Finnish (FIN) AF: 0.0746 AC: 792 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0904 AC: 6145 AN: 68008

Other (OTH) AF: 0.100 AC: 212 AN: 2114

Alfa AF: 0.0929 Hom.: 2348

Bravo AF: 0.0855

Asia WGS AF: 0.193 AC: 670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.85
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: rs11191580; hg19: chr10-104906211;