rs72843997

Variant names:

• chr10-103093533-A-G
• rs72843997
• NM_001351169.2:c.989-224T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001351169.2(NT5C2):​c.989-224T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 152,276 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.042 (145 hom., cov: 32)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.430
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-103093533-A-G is Benign according to our data. Variant chr10-103093533-A-G is described in ClinVar as Benign. ClinVar VariationId is 1224033.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.989-224T>C		intron_variant	Intron 14 of 18	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.989-224T>C		intron_variant	Intron 14 of 18	1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6394 AN: 152158 Hom.: 145 Cov.: 32

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0601

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0522

Gnomad OTH AF: 0.0431

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

GnomAD4 genome AF: 0.0420 AC: 6400 AN: 152276 Hom.: 145 Cov.: 32 AF XY: 0.0414 AC XY: 3085 AN XY: 74462

African (AFR) AF: 0.0313 AC: 1301 AN: 41558

American (AMR) AF: 0.0333 AC: 509 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0155 AC: 75 AN: 4826

European-Finnish (FIN) AF: 0.0601 AC: 637 AN: 10606

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0522 AC: 3549 AN: 68012

Other (OTH) AF: 0.0445 AC: 94 AN: 2112

Alfa AF: 0.0487 Hom.: 31

Bravo AF: 0.0388

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs72843997; hg19: chr10-104853290;