NM_001351169.2:c.1212-82T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001351169.2(NT5C2):​c.1212-82T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 1,256,530 control chromosomes in the GnomAD database, including 8,082 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (880 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7202 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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):

• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-103091078-A-G is Benign according to our data. Variant chr10-103091078-A-G is described in ClinVar as Benign. ClinVar VariationId is 1295697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 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.1212-82T>C		intron	N/A	NP_001338098.1
	NT5C2	NM_001351170.2		c.1236-82T>C		intron	N/A	NP_001338099.1
	NT5C2	NM_001351171.2		c.1236-82T>C		intron	N/A	NP_001338100.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	ENST00000404739.8	TSL:1 MANE Select	c.1212-82T>C		intron	N/A	ENSP00000383960.3
	NT5C2	ENST00000343289.9	TSL:1	c.1212-82T>C		intron	N/A	ENSP00000339479.5
	NT5C2	ENST00000874311.1		c.1428-82T>C		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes AF: 0.0940 AC: 14302 AN: 152106 Hom.: 874 Cov.: 32

Gnomad AFR AF: 0.0598

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.0745

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0898

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.101 AC: 111048 AN: 1104304 Hom.: 7202 AF XY: 0.104 AC XY: 58508 AN XY: 564520

African (AFR) AF: 0.0535 AC: 1397 AN: 26100

American (AMR) AF: 0.202 AC: 8544 AN: 42354

Ashkenazi Jewish (ASJ) AF: 0.0754 AC: 1796 AN: 23810

East Asian (EAS) AF: 0.262 AC: 9665 AN: 36942

South Asian (SAS) AF: 0.196 AC: 15233 AN: 77644

European-Finnish (FIN) AF: 0.0771 AC: 3015 AN: 39080

Middle Eastern (MID) AF: 0.0913 AC: 468 AN: 5128

European-Non Finnish (NFE) AF: 0.0821 AC: 66006 AN: 804300

Other (OTH) AF: 0.101 AC: 4924 AN: 48946

GnomAD4 genome AF: 0.0941 AC: 14322 AN: 152226 Hom.: 880 Cov.: 32 AF XY: 0.0960 AC XY: 7146 AN XY: 74430

African (AFR) AF: 0.0599 AC: 2491 AN: 41552

American (AMR) AF: 0.138 AC: 2112 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3470

East Asian (EAS) AF: 0.279 AC: 1443 AN: 5168

South Asian (SAS) AF: 0.182 AC: 879 AN: 4820

European-Finnish (FIN) AF: 0.0745 AC: 790 AN: 10604

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0898 AC: 6108 AN: 68008

Other (OTH) AF: 0.104 AC: 219 AN: 2110

Alfa AF: 0.0896 Hom.: 97

Bravo AF: 0.0979

Asia WGS AF: 0.196 AC: 680 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.1
DANN	Benign	0.62
PhyloP100		0.40
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: rs11191551; hg19: chr10-104850835; COSMIC: COSV58415379; COSMIC: COSV58415379;