Genetic Variant NT5E:c.-396G>C (chr6-85449744-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000369651.7(NT5E):c.-396G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 213,556 control chromosomes in the GnomAD database, including 3,697 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 3053 hom., cov: 32)

Exomes 𝑓: 0.13 ( 644 hom. )

Consequence

NT5E
ENST00000369651.7 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.17

Publications

9 publications found

Variant links:

Genes affected

NT5E (HGNC:8021): (5'-nucleotidase ecto) The protein encoded by this gene is a plasma membrane protein that catalyzes the conversion of extracellular nucleotides to membrane-permeable nucleosides. The encoded protein is used as a determinant of lymphocyte differentiation. Defects in this gene can lead to the calcification of joints and arteries. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

NT5E Gene-Disease associations (from GenCC):

hereditary arterial and articular multiple calcification syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

NT5E links:

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new If you want to explore the variant's impact on the transcript ENST00000369651.7, 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369651.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5E	ENST00000369651.7	TSL:2	c.-396G>C		5_prime_UTR	Exon 1 of 8	ENSP00000358665.3	P21589-2

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

28031

AN:

152104

Hom.:

3052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.0616

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.106

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.166

GnomAD4 exome

AF:

0.130

AC:

7950

AN:

61332

Hom.:

644

Cov.:

AF XY:

0.130

AC XY:

3950

AN XY:

30490

show subpopulations

African (AFR)

AF:

0.278

AC:

387

AN:

1394

American (AMR)

AF:

0.0994

AC:

108

AN:

1086

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

293

AN:

2024

East Asian (EAS)

AF:

0.0486

AC:

118

AN:

2430

South Asian (SAS)

AF:

0.151

AC:

708

AN:

4680

European-Finnish (FIN)

AF:

0.0915

AC:

348

AN:

3802

Middle Eastern (MID)

AF:

0.187

AC:

AN:

326

European-Non Finnish (NFE)

AF:

0.129

AC:

5361

AN:

41424

Other (OTH)

AF:

0.136

AC:

566

AN:

4166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

333

666

998

1331

1664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<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:

0.184

AC:

28054

AN:

152224

Hom.:

3053

Cov.:

AF XY:

0.179

AC XY:

13349

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.303

AC:

12586

AN:

41522

American (AMR)

AF:

0.132

AC:

2019

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

555

AN:

3468

East Asian (EAS)

AF:

0.0616

AC:

318

AN:

5166

South Asian (SAS)

AF:

0.168

AC:

813

AN:

4834

European-Finnish (FIN)

AF:

0.106

AC:

1126

AN:

10624

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.149

AC:

10099

AN:

68000

Other (OTH)

AF:

0.166

AC:

351

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1141

2282

3423

4564

5705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<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.:

322

Bravo

AF:

0.189

Asia WGS

AF:

0.116

AC:

403

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.0

(source)

DANN

Benign

0.52

PhyloP100

-2.2

PromoterAI

-0.091

Neutral

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over