Genetic Variant NM_001351169.2:c.1159+232_1159+236dupAAGTT (chr10-103092902-A-AAACTT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001351169.2(NT5C2):c.1159+232_1159+236dupAAGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.31 ( 7387 hom., cov: 0)

Consequence

NT5C2
NM_001351169.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.19

Publications

0 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 -10 ACMG points.

BP6

Variant 10-103092902-A-AAACTT is Benign according to our data. Variant chr10-103092902-A-AAACTT is described in ClinVar as Benign. ClinVar VariationId is 667740.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.32 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.1159+232_1159+236dupAAGTT	intron	N/A	NP_001338098.1	P49902-1
NT5C2	NM_001351170.2		c.1183+232_1183+236dupAAGTT	intron	N/A	NP_001338099.1	A0A6Q8PHP0
NT5C2	NM_001351171.2		c.1183+232_1183+236dupAAGTT	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.1159+236_1159+237insAAGTT	intron	N/A	ENSP00000383960.3	P49902-1
NT5C2	ENST00000343289.9	TSL:1	c.1159+236_1159+237insAAGTT	intron	N/A	ENSP00000339479.5	P49902-1
NT5C2	ENST00000874311.1		c.1375+236_1375+237insAAGTT	intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes

AF:

0.311

AC:

47206

AN:

151644

Hom.:

7382

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.363

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.324

Gnomad OTH

AF:

0.315

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.311

AC:

47240

AN:

151764

Hom.:

7387

Cov.:

AF XY:

0.308

AC XY:

22860

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.318

AC:

13159

AN:

41374

American (AMR)

AF:

0.264

AC:

4027

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.363

AC:

1257

AN:

3466

East Asian (EAS)

AF:

0.273

AC:

1409

AN:

5154

South Asian (SAS)

AF:

0.265

AC:

1275

AN:

4818

European-Finnish (FIN)

AF:

0.291

AC:

3059

AN:

10528

Middle Eastern (MID)

AF:

0.360

AC:

105

AN:

292

European-Non Finnish (NFE)

AF:

0.324

AC:

21988

AN:

67852

Other (OTH)

AF:

0.316

AC:

665

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1642

3284

4926

6568

8210

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:

0.165

Hom.:

305

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over