dbSNP rs10883830: NT5C2:c.1211+36C>T (chr10-103091528-G-A) – 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.1211+36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,508,384 control chromosomes in the GnomAD database, including 71,359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7541 hom., cov: 32)

Exomes 𝑓: 0.30 ( 63818 hom. )

Consequence

NT5C2
NM_001351169.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.363

Publications

12 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

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=-0.94).

BP6

Variant 10-103091528-G-A is Benign according to our data. Variant chr10-103091528-G-A is described in ClinVar as Benign. ClinVar VariationId is 667762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 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.1211+36C>T	intron	N/A	NP_001338098.1	P49902-1
NT5C2	NM_001351170.2		c.1235+36C>T	intron	N/A	NP_001338099.1	A0A6Q8PHP0
NT5C2	NM_001351171.2		c.1235+36C>T	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.1211+36C>T	intron	N/A	ENSP00000383960.3	P49902-1
NT5C2	ENST00000343289.9	TSL:1	c.1211+36C>T	intron	N/A	ENSP00000339479.5	P49902-1
NT5C2	ENST00000874311.1		c.1427+36C>T	intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47410

AN:

152008

Hom.:

7535

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.314

GnomAD2 exomes

AF:

0.285

AC:

70978

AN:

248614

AF XY:

0.287

show subpopulations

Gnomad AFR exome

AF:

0.327

Gnomad AMR exome

AF:

0.206

Gnomad ASJ exome

AF:

0.347

Gnomad EAS exome

AF:

0.210

Gnomad FIN exome

AF:

0.288

Gnomad NFE exome

AF:

0.321

Gnomad OTH exome

AF:

0.302

GnomAD4 exome

AF:

0.303

AC:

410742

AN:

1356258

Hom.:

63818

Cov.:

AF XY:

0.301

AC XY:

205232

AN XY:

680744

show subpopulations

African (AFR)

AF:

0.333

AC:

10372

AN:

31174

American (AMR)

AF:

0.214

AC:

9374

AN:

43882

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

8750

AN:

25382

East Asian (EAS)

AF:

0.159

AC:

6198

AN:

39048

South Asian (SAS)

AF:

0.242

AC:

20081

AN:

83064

European-Finnish (FIN)

AF:

0.288

AC:

15292

AN:

53160

Middle Eastern (MID)

AF:

0.344

AC:

1821

AN:

5294

European-Non Finnish (NFE)

AF:

0.316

AC:

321432

AN:

1018478

Other (OTH)

AF:

0.307

AC:

17422

AN:

56776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

13237

26474

39712

52949

66186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9916

19832

29748

39664

49580

<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:

0.312

AC:

47441

AN:

152126

Hom.:

7541

Cov.:

AF XY:

0.307

AC XY:

22853

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.328

AC:

13620

AN:

41486

American (AMR)

AF:

0.265

AC:

4046

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.361

AC:

1253

AN:

3468

East Asian (EAS)

AF:

0.207

AC:

1072

AN:

5180

South Asian (SAS)

AF:

0.245

AC:

1184

AN:

4824

European-Finnish (FIN)

AF:

0.290

AC:

3064

AN:

10562

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.325

AC:

22129

AN:

67996

Other (OTH)

AF:

0.314

AC:

663

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1684

3368

5052

6736

8420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<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:

0.327

Hom.:

3363

Bravo

AF:

0.310

Asia WGS

AF:

0.227

AC:

787

AN:

3478

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

-0.94

CADD

Benign

2.7

(source)

DANN

Benign

0.30

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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