10-103091078-A-C

Variant names:

• chr10-103091078-A-C
• rs11191551
• NM_001351169.2:c.1212-82T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001351169.2(NT5C2):​c.1212-82T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000271 in 1,105,114 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.403
• Publications: 21 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.1212-82T>G		intron	N/A	NP_001338098.1	P49902-1
	NT5C2	NM_001351170.2		c.1236-82T>G		intron	N/A	NP_001338099.1	A0A6Q8PHP0
	NT5C2	NM_001351171.2		c.1236-82T>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.1212-82T>G		intron	N/A	ENSP00000383960.3	P49902-1
	NT5C2	ENST00000343289.9	TSL:1	c.1212-82T>G		intron	N/A	ENSP00000339479.5	P49902-1
	NT5C2	ENST00000874311.1		c.1428-82T>G		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000271 AC: 3 AN: 1105114 Hom.: 0 AF XY: 0.00000531 AC XY: 3 AN XY: 564906

African (AFR) AF: 0.00 AC: 0 AN: 26112

American (AMR) AF: 0.00 AC: 0 AN: 42406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23816

East Asian (EAS) AF: 0.0000812 AC: 3 AN: 36964

South Asian (SAS) AF: 0.00 AC: 0 AN: 77694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5128

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 804912

Other (OTH) AF: 0.00 AC: 0 AN: 48980

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.61
PhyloP100		0.40

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11191551;

hg19: chr10-104850835;