rs11191582

Variant names:

• chr10-103153896-G-A
• rs11191582
• NM_001351169.2:c.102-14417C>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.102-14417C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0725 in 623,274 control chromosomes in the GnomAD database, including 2,295 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 0.082 (777 hom., cov: 32)
  • Exomes 𝑓: 0.069 (1518 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 35 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.102-14417C>T		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.102-14417C>T		intron_variant	Intron 3 of 18	1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12472 AN: 152088 Hom.: 773 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0720

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0746

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0903

Gnomad OTH AF: 0.0967

GnomAD4 exome AF: 0.0695 AC: 32719 AN: 471068 Hom.: 1518 AF XY: 0.0697 AC XY: 15413 AN XY: 221168

African (AFR) AF: 0.00862 AC: 76 AN: 8818

American (AMR) AF: 0.159 AC: 83 AN: 522

Ashkenazi Jewish (ASJ) AF: 0.0662 AC: 198 AN: 2992

East Asian (EAS) AF: 0.234 AC: 444 AN: 1900

South Asian (SAS) AF: 0.188 AC: 1641 AN: 8742

European-Finnish (FIN) AF: 0.0617 AC: 10 AN: 162

Middle Eastern (MID) AF: 0.0762 AC: 71 AN: 932

European-Non Finnish (NFE) AF: 0.0670 AC: 28940 AN: 431714

Other (OTH) AF: 0.0822 AC: 1256 AN: 15286

GnomAD4 genome AF: 0.0820 AC: 12482 AN: 152206 Hom.: 777 Cov.: 32 AF XY: 0.0845 AC XY: 6290 AN XY: 74416

African (AFR) AF: 0.0201 AC: 833 AN: 41536

American (AMR) AF: 0.134 AC: 2043 AN: 15278

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

East Asian (EAS) AF: 0.251 AC: 1301 AN: 5176

South Asian (SAS) AF: 0.182 AC: 877 AN: 4828

European-Finnish (FIN) AF: 0.0746 AC: 791 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0903 AC: 6140 AN: 67994

Other (OTH) AF: 0.0995 AC: 210 AN: 2110

Alfa AF: 0.0596 Hom.: 96

Bravo AF: 0.0838

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.7
DANN	Benign	0.52
PhyloP100		-0.23
PromoterAI		-0.13	Neutral
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: rs11191582; hg19: chr10-104913653;