rs1057519866

Variant names:

• chr10-103093198-C-T
• rs1057519866
• NM_001351169.2:c.1100G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001351169.2(NT5C2):​c.1100G>A​(p.Arg367Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NT5C2 NM_001351169.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.90
• Publications: 42 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.885

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.1100G>A	p.Arg367Gln	missense_variant	Exon 15 of 19	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.1100G>A	p.Arg367Gln	missense_variant	Exon 15 of 19	1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459520 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725992

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 85552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110952

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.41	T;T;.
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D;D
M_CAP	Uncertain	0.096	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Benign	-0.33	T
MutationAssessor	Pathogenic	3.2	M;M;.
PhyloP100		7.9
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.0040	D;D;.
Polyphen		1.0	D;D;.
Vest4		0.90
MutPred		0.81		Loss of MoRF binding (P = 0.0142);Loss of MoRF binding (P = 0.0142);.;
MVP		0.72
MPC		1.6
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.86
gMVP		0.72
Mutation Taster		=45/55	disease causing

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: rs1057519866; hg19: chr10-104852955; COSMIC: COSV58414509; COSMIC: COSV58414509;