10-103092902-AAACTT-AAACTTAACTT

Variant names:

• chr10-103092902-A-AAACTT
• rs3837340
• NM_001351169.2:c.1159+232_1159+236dupAAGTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001351169.2(NT5C2):​c.1159+232_1159+236dupAAGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7387 hom., cov: 0)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.19
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 10-103092902-A-AAACTT is Benign according to our data. Variant chr10-103092902-A-AAACTT is described in ClinVar as Benign. ClinVar VariationId is 667740.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 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.1159+232_1159+236dupAAGTT		intron	N/A	NP_001338098.1	P49902-1
	NT5C2	NM_001351170.2		c.1183+232_1183+236dupAAGTT		intron	N/A	NP_001338099.1	A0A6Q8PHP0
	NT5C2	NM_001351171.2		c.1183+232_1183+236dupAAGTT		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.1159+236_1159+237insAAGTT		intron	N/A	ENSP00000383960.3	P49902-1
	NT5C2	ENST00000343289.9	TSL:1	c.1159+236_1159+237insAAGTT		intron	N/A	ENSP00000339479.5	P49902-1
	NT5C2	ENST00000874311.1		c.1375+236_1375+237insAAGTT		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47206 AN: 151644 Hom.: 7382 Cov.: 0

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.311 AC: 47240 AN: 151764 Hom.: 7387 Cov.: 0 AF XY: 0.308 AC XY: 22860 AN XY: 74188

African (AFR) AF: 0.318 AC: 13159 AN: 41374

American (AMR) AF: 0.264 AC: 4027 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1257 AN: 3466

East Asian (EAS) AF: 0.273 AC: 1409 AN: 5154

South Asian (SAS) AF: 0.265 AC: 1275 AN: 4818

European-Finnish (FIN) AF: 0.291 AC: 3059 AN: 10528

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.324 AC: 21988 AN: 67852

Other (OTH) AF: 0.316 AC: 665 AN: 2106

Alfa AF: 0.165 Hom.: 305

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3837340; hg19: chr10-104852659;