rs11191553

Variant names:

• chr10-103091639-G-T
• rs11191553
• NM_001351169.2:c.1160-24C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001351169.2(NT5C2):​c.1160-24C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,597,430 control chromosomes in the GnomAD database, including 75,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7526 hom., cov: 33)
  • Exomes 𝑓: 0.30 (67925 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.557
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 10-103091639-G-T is Benign according to our data. Variant chr10-103091639-G-T is described in ClinVar as Benign. ClinVar VariationId is 667744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.1160-24C>A		intron_variant	Intron 15 of 18	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.1160-24C>A		intron_variant	Intron 15 of 18	1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47383 AN: 151966 Hom.: 7520 Cov.: 33

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.314

GnomAD2 exomes AF: 0.286 AC: 71529 AN: 250322 AF XY: 0.287

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.211

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.304

GnomAD4 exome AF: 0.302 AC: 436583 AN: 1445346 Hom.: 67925 Cov.: 27 AF XY: 0.301 AC XY: 216570 AN XY: 719950

African (AFR) AF: 0.332 AC: 10971 AN: 33030

American (AMR) AF: 0.214 AC: 9516 AN: 44416

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 8944 AN: 25962

East Asian (EAS) AF: 0.159 AC: 6284 AN: 39574

South Asian (SAS) AF: 0.241 AC: 20682 AN: 85708

European-Finnish (FIN) AF: 0.288 AC: 15312 AN: 53230

Middle Eastern (MID) AF: 0.348 AC: 1989 AN: 5720

European-Non Finnish (NFE) AF: 0.314 AC: 344573 AN: 1097916

Other (OTH) AF: 0.306 AC: 18312 AN: 59790

GnomAD4 genome AF: 0.312 AC: 47414 AN: 152084 Hom.: 7526 Cov.: 33 AF XY: 0.307 AC XY: 22857 AN XY: 74360

African (AFR) AF: 0.328 AC: 13611 AN: 41492

American (AMR) AF: 0.264 AC: 4040 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1254 AN: 3468

East Asian (EAS) AF: 0.207 AC: 1069 AN: 5170

South Asian (SAS) AF: 0.245 AC: 1181 AN: 4824

European-Finnish (FIN) AF: 0.290 AC: 3067 AN: 10570

Middle Eastern (MID) AF: 0.366 AC: 107 AN: 292

European-Non Finnish (NFE) AF: 0.325 AC: 22120 AN: 67964

Other (OTH) AF: 0.314 AC: 662 AN: 2108

Alfa AF: 0.320 Hom.: 10312

Bravo AF: 0.310

Asia WGS AF: 0.227 AC: 788 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	15
DANN	Benign	0.80
PhyloP100		0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11191553; hg19: chr10-104851396; COSMIC: COSV58414866; COSMIC: COSV58414866;