rs10883830

Variant names:

• chr10-103091528-G-A
• rs10883830
• NM_001351169.2:c.1211+36C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-103091528-G-A
• chr10-103091528-G-C
• chr10-103091528-G-T

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.1211+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,508,384 control chromosomes in the GnomAD database, including 71,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7541 hom., cov: 32)
  • Exomes 𝑓: 0.30 (63818 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.363
• Publications: 12 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=-0.94).
• BP6: Variant 10-103091528-G-A is Benign according to our data. Variant chr10-103091528-G-A is described in ClinVar as Benign. ClinVar VariationId is 667762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	NM_001351169.2	MANE Select	c.1211+36C>T		intron	N/A	NP_001338098.1
	NT5C2	NM_001351170.2		c.1235+36C>T		intron	N/A	NP_001338099.1
	NT5C2	NM_001351171.2		c.1235+36C>T		intron	N/A	NP_001338100.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	ENST00000404739.8	TSL:1 MANE Select	c.1211+36C>T		intron	N/A	ENSP00000383960.3
	NT5C2	ENST00000343289.9	TSL:1	c.1211+36C>T		intron	N/A	ENSP00000339479.5
	NT5C2	ENST00000674860.1		c.1235+36C>T		intron	N/A	ENSP00000502816.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47410 AN: 152008 Hom.: 7535 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.314

GnomAD2 exomes AF: 0.285 AC: 70978 AN: 248614 AF XY: 0.287

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.347

Gnomad EAS exome AF: 0.210

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.302

GnomAD4 exome AF: 0.303 AC: 410742 AN: 1356258 Hom.: 63818 Cov.: 20 AF XY: 0.301 AC XY: 205232 AN XY: 680744

African (AFR) AF: 0.333 AC: 10372 AN: 31174

American (AMR) AF: 0.214 AC: 9374 AN: 43882

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 8750 AN: 25382

East Asian (EAS) AF: 0.159 AC: 6198 AN: 39048

South Asian (SAS) AF: 0.242 AC: 20081 AN: 83064

European-Finnish (FIN) AF: 0.288 AC: 15292 AN: 53160

Middle Eastern (MID) AF: 0.344 AC: 1821 AN: 5294

European-Non Finnish (NFE) AF: 0.316 AC: 321432 AN: 1018478

Other (OTH) AF: 0.307 AC: 17422 AN: 56776

GnomAD4 genome AF: 0.312 AC: 47441 AN: 152126 Hom.: 7541 Cov.: 32 AF XY: 0.307 AC XY: 22853 AN XY: 74368

African (AFR) AF: 0.328 AC: 13620 AN: 41486

American (AMR) AF: 0.265 AC: 4046 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3468

East Asian (EAS) AF: 0.207 AC: 1072 AN: 5180

South Asian (SAS) AF: 0.245 AC: 1184 AN: 4824

European-Finnish (FIN) AF: 0.290 AC: 3064 AN: 10562

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22129 AN: 67996

Other (OTH) AF: 0.314 AC: 663 AN: 2114

Alfa AF: 0.327 Hom.: 3363

Bravo AF: 0.310

Asia WGS AF: 0.227 AC: 787 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.7
DANN	Benign	0.30
PhyloP100		0.36
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: rs10883830; hg19: chr10-104851285; COSMIC: COSV107447614; COSMIC: COSV107447614;