rs4917996

Variant names:

• chr10-103166072-A-C
• rs4917996
• NM_001351169.2:c.101+8786T>G

Variant summary

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

The NM_001351169.2(NT5C2):​c.101+8786T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,170 control chromosomes in the GnomAD database, including 12,996 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 0.41 (12996 hom., cov: 34)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540
• Publications: 9 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: 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	NM_001351169.2	MANE Select	c.101+8786T>G		intron	N/A	NP_001338098.1	P49902-1
	NT5C2	NM_001351170.2		c.101+8786T>G		intron	N/A	NP_001338099.1	A0A6Q8PHP0
	NT5C2	NM_001351171.2		c.101+8786T>G		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.101+8786T>G		intron	N/A	ENSP00000383960.3	P49902-1
	NT5C2	ENST00000343289.9	TSL:1	c.101+8786T>G		intron	N/A	ENSP00000339479.5	P49902-1
	NT5C2	ENST00000874311.1		c.101+8786T>G		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62317 AN: 152052 Hom.: 12982 Cov.: 34

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.410 AC: 62374 AN: 152170 Hom.: 12996 Cov.: 34 AF XY: 0.408 AC XY: 30372 AN XY: 74386

African (AFR) AF: 0.389 AC: 16169 AN: 41548

American (AMR) AF: 0.403 AC: 6158 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1508 AN: 3468

East Asian (EAS) AF: 0.558 AC: 2882 AN: 5166

South Asian (SAS) AF: 0.449 AC: 2169 AN: 4828

European-Finnish (FIN) AF: 0.367 AC: 3878 AN: 10566

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28268 AN: 67986

Other (OTH) AF: 0.423 AC: 896 AN: 2116

Alfa AF: 0.410 Hom.: 3651

Bravo AF: 0.412

Asia WGS AF: 0.467 AC: 1619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.52
PhyloP100		-0.054
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: rs4917996; hg19: chr10-104925829;