rs73353837

Variant names:

• chr10-103099073-C-T
• rs73353837
• NM_001351169.2:c.634-89G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001351169.2(NT5C2):​c.634-89G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,009,286 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (41 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (26 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.319
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-103099073-C-T is Benign according to our data. Variant chr10-103099073-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1209471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0128 (1953/152218) while in subpopulation AFR AF = 0.0429 (1780/41522). AF 95% confidence interval is 0.0412. There are 41 homozygotes in GnomAd4. There are 908 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 41 AR gene

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.634-89G>A		intron	N/A	NP_001338098.1	P49902-1
	NT5C2	NM_001351170.2		c.658-89G>A		intron	N/A	NP_001338099.1	A0A6Q8PHP0
	NT5C2	NM_001351171.2		c.658-89G>A		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.634-89G>A		intron	N/A	ENSP00000383960.3	P49902-1
	NT5C2	ENST00000343289.9	TSL:1	c.634-89G>A		intron	N/A	ENSP00000339479.5	P49902-1
	NT5C2	ENST00000874311.1		c.850-89G>A		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1952 AN: 152100 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0144

GnomAD4 exome AF: 0.00164 AC: 1406 AN: 857068 Hom.: 26 AF XY: 0.00143 AC XY: 632 AN XY: 443310

African (AFR) AF: 0.0429 AC: 848 AN: 19776

American (AMR) AF: 0.00371 AC: 109 AN: 29386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21238

East Asian (EAS) AF: 0.00169 AC: 56 AN: 33088

South Asian (SAS) AF: 0.000316 AC: 21 AN: 66462

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46924

Middle Eastern (MID) AF: 0.00384 AC: 12 AN: 3128

European-Non Finnish (NFE) AF: 0.000352 AC: 210 AN: 597304

Other (OTH) AF: 0.00377 AC: 150 AN: 39762

GnomAD4 genome AF: 0.0128 AC: 1953 AN: 152218 Hom.: 41 Cov.: 32 AF XY: 0.0122 AC XY: 908 AN XY: 74412

African (AFR) AF: 0.0429 AC: 1780 AN: 41522

American (AMR) AF: 0.00693 AC: 106 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68020

Other (OTH) AF: 0.0142 AC: 30 AN: 2110

Alfa AF: 0.00942 Hom.: 18

Bravo AF: 0.0145

Asia WGS AF: 0.00346 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.46
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism

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: rs73353837; hg19: chr10-104858830;