rs41287482

Variant names:

• chr10-103101176-A-G
• rs41287482
• NM_001351169.2:c.481+59T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001351169.2(NT5C2):​c.481+59T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,409,854 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (12 hom., cov: 32)
  • Exomes 𝑓: 0.014 (175 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.02
• Publications: 3 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):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 45

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 10-103101176-A-G is Benign according to our data. Variant chr10-103101176-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1213606.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0101 (1528/151900) while in subpopulation NFE AF = 0.0168 (1146/68024). AF 95% confidence interval is 0.016. There are 12 homozygotes in GnomAd4. There are 704 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	NM_001351169.2	MANE Select	c.481+59T>C		intron	N/A	NP_001338098.1	P49902-1
	NT5C2	NM_001351170.2		c.505+59T>C		intron	N/A	NP_001338099.1	A0A6Q8PHP0
	NT5C2	NM_001351171.2		c.505+59T>C		intron	N/A	NP_001338100.1	A0A6Q8PHP0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	ENST00000404739.8	TSL:1 MANE Select	c.481+59T>C		intron	N/A	ENSP00000383960.3	P49902-1
	NT5C2	ENST00000343289.9	TSL:1	c.481+59T>C		intron	N/A	ENSP00000339479.5	P49902-1
	NT5C2	ENST00000874311.1		c.697+59T>C		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1530 AN: 151786 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00324

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00787

Gnomad FIN AF: 0.00678

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0169

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.0145 AC: 18220 AN: 1257954 Hom.: 175 Cov.: 18 AF XY: 0.0143 AC XY: 9076 AN XY: 636770

African (AFR) AF: 0.00236 AC: 69 AN: 29184

American (AMR) AF: 0.00427 AC: 188 AN: 44026

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 328 AN: 24854

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38688

South Asian (SAS) AF: 0.00847 AC: 693 AN: 81810

European-Finnish (FIN) AF: 0.00940 AC: 501 AN: 53276

Middle Eastern (MID) AF: 0.00985 AC: 53 AN: 5382

European-Non Finnish (NFE) AF: 0.0170 AC: 15742 AN: 927210

Other (OTH) AF: 0.0121 AC: 645 AN: 53524

GnomAD4 genome AF: 0.0101 AC: 1528 AN: 151900 Hom.: 12 Cov.: 32 AF XY: 0.00948 AC XY: 704 AN XY: 74296

African (AFR) AF: 0.00323 AC: 133 AN: 41174

American (AMR) AF: 0.00425 AC: 65 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00767 AC: 37 AN: 4824

European-Finnish (FIN) AF: 0.00678 AC: 72 AN: 10616

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.0168 AC: 1146 AN: 68024

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.0143 Hom.: 4

Bravo AF: 0.00960

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	17
DANN	Benign	0.71
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism

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: rs41287482; hg19: chr10-104860933;