dbSNP rs1926030: NT5C2:c.813+40A>G (chr10-103095899-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001351169.2(NT5C2):c.813+40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,532,738 control chromosomes in the GnomAD database, including 123,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 13016 hom., cov: 31)

Exomes 𝑓: 0.40 ( 110720 hom. )

Consequence

NT5C2
NM_001351169.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.104

Publications

22 publications found

Variant links:

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

NT5C2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001351169.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-103095899-T-C is Benign according to our data. Variant chr10-103095899-T-C is described in ClinVar as Benign. ClinVar VariationId is 1235346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NT5C2	NM_001351169.2	MANE Select	c.813+40A>G	intron	N/A	NP_001338098.1	P49902-1
NT5C2	NM_001351170.2		c.837+40A>G	intron	N/A	NP_001338099.1	A0A6Q8PHP0
NT5C2	NM_001351171.2		c.837+40A>G	intron	N/A	NP_001338100.1	A0A6Q8PHP0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NT5C2	ENST00000404739.8	TSL:1 MANE Select	c.813+40A>G	intron	N/A	ENSP00000383960.3	P49902-1
NT5C2	ENST00000343289.9	TSL:1	c.813+40A>G	intron	N/A	ENSP00000339479.5	P49902-1
NT5C2	ENST00000874311.1		c.1029+40A>G	intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

62358

AN:

151846

Hom.:

13003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.389

Gnomad AMI

AF:

0.350

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.440

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.368

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.417

Gnomad OTH

AF:

0.421

GnomAD2 exomes

AF:

0.423

AC:

105460

AN:

249090

AF XY:

0.425

show subpopulations

Gnomad AFR exome

AF:

0.386

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.433

Gnomad EAS exome

AF:

0.564

Gnomad FIN exome

AF:

0.374

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.420

GnomAD4 exome

AF:

0.397

AC:

548607

AN:

1380772

Hom.:

110720

Cov.:

AF XY:

0.400

AC XY:

276585

AN XY:

691476

show subpopulations

African (AFR)

AF:

0.380

AC:

12070

AN:

31738

American (AMR)

AF:

0.419

AC:

18543

AN:

44214

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

10941

AN:

25596

East Asian (EAS)

AF:

0.501

AC:

19685

AN:

39282

South Asian (SAS)

AF:

0.455

AC:

38280

AN:

84182

European-Finnish (FIN)

AF:

0.373

AC:

19912

AN:

53322

Middle Eastern (MID)

AF:

0.437

AC:

2455

AN:

5624

European-Non Finnish (NFE)

AF:

0.388

AC:

403183

AN:

1039148

Other (OTH)

AF:

0.408

AC:

23538

AN:

57666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

13938

27875

41813

55750

69688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12108

24216

36324

48432

60540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.411

AC:

62414

AN:

151966

Hom.:

13016

Cov.:

AF XY:

0.409

AC XY:

30381

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.389

AC:

16127

AN:

41444

American (AMR)

AF:

0.404

AC:

6176

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.440

AC:

1527

AN:

3468

East Asian (EAS)

AF:

0.557

AC:

2884

AN:

5176

South Asian (SAS)

AF:

0.450

AC:

2164

AN:

4814

European-Finnish (FIN)

AF:

0.368

AC:

3882

AN:

10548

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.417

AC:

28310

AN:

67914

Other (OTH)

AF:

0.424

AC:

896

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1881

3762

5643

7524

9405

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.416

Hom.:

16448

Bravo

AF:

0.412

Asia WGS

AF:

0.465

AC:

1614

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.0

(source)

DANN

Benign

0.43

PhyloP100

-0.10

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over