Genetic Variant NT5C2:c.1272+73T>G (chr10-103090863-A-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.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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.609

Publications

5 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):

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=-0.85).

BP6

Variant 10-103090863-A-C is Benign according to our data. Variant chr10-103090863-A-C is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2 link	c.1272+73T>G		intron_variant	Intron 17 of 18	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8 link	c.1272+73T>G		intron_variant	Intron 17 of 18	1	NM_001351169.2	ENSP00000383960.3		P49902-1

Frequencies

GnomAD3 genomes

AF:

0.0696

AC:

10557

AN:

151628

Hom.:

504

Cov.:

show subpopulations

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.:

AF XY:

0.0859

AC XY:

61706

AN XY:

718692

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

5871

11742

17612

23483

29354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0695

AC:

10551

AN:

151746

Hom.:

504

Cov.:

AF XY:

0.0683

AC XY:

5066

AN XY:

74170

show subpopulations

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:

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.102

AC:

6933

AN:

67820

Other (OTH)

AF:

0.0716

AC:

151

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

509

1018

1528

2037

2546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0898

Hom.:

123

Bravo

AF:

0.0636

Asia WGS

AF:

0.0120

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 26, 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

-0.85

CADD

Benign

0.97

(source)

DANN

Benign

0.42

PhyloP100

-0.61

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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chr10-103090863-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over