NM_001351169.2:c.1272+73T>G

Variant names:

• chr10-103090863-A-C
• rs34758128
• NM_001351169.2:c.1272+73T>G

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.1272+73T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0857 in 1,594,456 control chromosomes in the GnomAD database, including 6,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (504 hom., cov: 32)
  • Exomes 𝑓: 0.087 (6289 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.609
• Publications: 5 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=-0.85).
• BP6: Variant 10-103090863-A-C is Benign according to our data. Variant chr10-103090863-A-C is described in ClinVar as Benign. ClinVar VariationId is 1237292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.1 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	NM_001351169.2	MANE Select	c.1272+73T>G		intron	N/A	NP_001338098.1
	NT5C2	NM_001351170.2		c.1296+73T>G		intron	N/A	NP_001338099.1
	NT5C2	NM_001351171.2		c.1296+73T>G		intron	N/A	NP_001338100.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	ENST00000404739.8	TSL:1 MANE Select	c.1272+73T>G		intron	N/A	ENSP00000383960.3
	NT5C2	ENST00000343289.9	TSL:1	c.1272+73T>G		intron	N/A	ENSP00000339479.5
	NT5C2	ENST00000674860.1		c.1296+73T>G		intron	N/A	ENSP00000502816.1

Frequencies

GnomAD3 genomes AF: 0.0696 AC: 10557 AN: 151628 Hom.: 504 Cov.: 32

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0543

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.0728

GnomAD4 exome AF: 0.0874 AC: 126044 AN: 1442710 Hom.: 6289 Cov.: 26 AF XY: 0.0859 AC XY: 61706 AN XY: 718692

African (AFR) AF: 0.0177 AC: 585 AN: 32964

American (AMR) AF: 0.0437 AC: 1936 AN: 44274

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2893 AN: 25918

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39618

South Asian (SAS) AF: 0.0212 AC: 1812 AN: 85468

European-Finnish (FIN) AF: 0.100 AC: 5347 AN: 53246

Middle Eastern (MID) AF: 0.0320 AC: 183 AN: 5722

European-Non Finnish (NFE) AF: 0.0992 AC: 108673 AN: 1095780

Other (OTH) AF: 0.0771 AC: 4606 AN: 59720

GnomAD4 genome AF: 0.0695 AC: 10551 AN: 151746 Hom.: 504 Cov.: 32 AF XY: 0.0683 AC XY: 5066 AN XY: 74170

African (AFR) AF: 0.0227 AC: 938 AN: 41394

American (AMR) AF: 0.0541 AC: 826 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3456

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0231 AC: 111 AN: 4810

European-Finnish (FIN) AF: 0.102 AC: 1078 AN: 10528

Middle Eastern (MID) AF: 0.0377 AC: 11 AN: 292

European-Non Finnish (NFE) AF: 0.102 AC: 6933 AN: 67820

Other (OTH) AF: 0.0716 AC: 151 AN: 2110

Alfa AF: 0.0898 Hom.: 123

Bravo AF: 0.0636

Asia WGS AF: 0.0120 AC: 41 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.97
DANN	Benign	0.42
PhyloP100		-0.61
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: rs34758128; hg19: chr10-104850620;