rs11191557

Variant names:

• chr10-103104857-C-G
• rs11191557
• NM_001351169.2:c.389+849G>C

Variant summary

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

The NM_001351169.2(NT5C2):​c.389+849G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0887 in 152,176 control chromosomes in the GnomAD database, including 839 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 (839 hom., cov: 32)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.587
• Publications: 21 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.389+849G>C		intron_variant	Intron 6 of 18	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.389+849G>C		intron_variant	Intron 6 of 18	1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes AF: 0.0886 AC: 13475 AN: 152058 Hom.: 834 Cov.: 32

Gnomad AFR AF: 0.0396

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0749

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0903

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0887 AC: 13491 AN: 152176 Hom.: 839 Cov.: 32 AF XY: 0.0909 AC XY: 6760 AN XY: 74382

African (AFR) AF: 0.0397 AC: 1648 AN: 41536

American (AMR) AF: 0.136 AC: 2078 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3468

East Asian (EAS) AF: 0.278 AC: 1436 AN: 5170

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

European-Finnish (FIN) AF: 0.0749 AC: 792 AN: 10580

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

European-Non Finnish (NFE) AF: 0.0903 AC: 6141 AN: 67994

Other (OTH) AF: 0.104 AC: 219 AN: 2112

Alfa AF: 0.0867 Hom.: 85

Bravo AF: 0.0915

Asia WGS AF: 0.194 AC: 673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.48
PhyloP100		0.59
Mutation Taster		=98/2	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: rs11191557; hg19: chr10-104864614;