dbSNP rs72843997: NT5C2:c.989-224T>C (chr10-103093533-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001351169.2(NT5C2):c.989-224T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.042 in 152,276 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.042 ( 145 hom., cov: 32)

Consequence

NT5C2
NM_001351169.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.430

Publications

2 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 10-103093533-A-G is Benign according to our data. Variant chr10-103093533-A-G is described in ClinVar as Benign. ClinVar VariationId is 1224033.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0507 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.989-224T>C	intron	N/A	NP_001338098.1	P49902-1
NT5C2	NM_001351170.2		c.1013-224T>C	intron	N/A	NP_001338099.1	A0A6Q8PHP0
NT5C2	NM_001351171.2		c.1013-224T>C	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.989-224T>C	intron	N/A	ENSP00000383960.3	P49902-1
NT5C2	ENST00000343289.9	TSL:1	c.989-224T>C	intron	N/A	ENSP00000339479.5	P49902-1
NT5C2	ENST00000874311.1		c.1205-224T>C	intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes

AF:

0.0420

AC:

6394

AN:

152158

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0314

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.0332

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0151

Gnomad FIN

AF:

0.0601

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0522

Gnomad OTH

AF:

0.0431

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

GnomAD4 genome

AF:

0.0420

AC:

6400

AN:

152276

Hom.:

145

Cov.:

AF XY:

0.0414

AC XY:

3085

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0313

AC:

1301

AN:

41558

American (AMR)

AF:

0.0333

AC:

509

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

117

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.0155

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0601

AC:

637

AN:

10606

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0522

AC:

3549

AN:

68012

Other (OTH)

AF:

0.0445

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

303

606

910

1213

1516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0487

Hom.:

Bravo

AF:

0.0388

Asia WGS

AF:

0.0150

AC:

AN:

3478

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

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.43

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over