10-103107201-A-G

Variant names:

• chr10-103107201-A-G
• rs7896547
• NM_001351169.2:c.176-495T>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.176-495T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,018 control chromosomes in the GnomAD database, including 13,033 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 (13033 hom., cov: 32)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.562
• Publications: 11 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=-0.93).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	NM_001351169.2	MANE Select	c.176-495T>C		intron	N/A	NP_001338098.1
	NT5C2	NM_001351170.2		c.176-495T>C		intron	N/A	NP_001338099.1
	NT5C2	NM_001351171.2		c.176-495T>C		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.176-495T>C		intron	N/A	ENSP00000383960.3
	NT5C2	ENST00000343289.9	TSL:1	c.176-495T>C		intron	N/A	ENSP00000339479.5
	NT5C2	ENST00000674860.1		c.176-495T>C		intron	N/A	ENSP00000502816.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62388 AN: 151900 Hom.: 13019 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.411 AC: 62446 AN: 152018 Hom.: 13033 Cov.: 32 AF XY: 0.409 AC XY: 30406 AN XY: 74312

African (AFR) AF: 0.391 AC: 16213 AN: 41446

American (AMR) AF: 0.403 AC: 6164 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1513 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2883 AN: 5168

South Asian (SAS) AF: 0.449 AC: 2166 AN: 4824

European-Finnish (FIN) AF: 0.368 AC: 3888 AN: 10564

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28276 AN: 67952

Other (OTH) AF: 0.425 AC: 894 AN: 2104

Alfa AF: 0.424 Hom.: 3961

Bravo AF: 0.413

Asia WGS AF: 0.468 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.4
DANN	Benign	0.51
PhyloP100		-0.56
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: rs7896547; hg19: chr10-104866958;