Genetic Variant NT5E:c.1211-77C>T (chr6-85490431-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_002526.4(NT5E):c.1211-77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 1,527,280 control chromosomes in the GnomAD database, including 267 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 0.014 ( 28 hom., cov: 33)

Exomes 𝑓: 0.018 ( 239 hom. )

Consequence

NT5E
NM_002526.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.63

Publications

1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

NT5E links:

Genome browser will be placed here

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=-0.86).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0139 (2110/152334) while in subpopulation NFE AF = 0.021 (1426/68022). AF 95% confidence interval is 0.0201. There are 28 homozygotes in GnomAd4. There are 1009 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5E	NM_002526.4 link	c.1211-77C>T		intron_variant	Intron 6 of 8	ENST00000257770.8	NP_002517.1	P21589-1Q6NZX3
NT5E	NM_001204813.2 link	c.1210+832C>T		intron_variant	Intron 6 of 7		NP_001191742.1	P21589-2Q6NZX3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NT5E	ENST00000257770.8 link	c.1211-77C>T	intron_variant	Intron 6 of 8	1	NM_002526.4	ENSP00000257770.3	P21589-1
NT5E	ENST00000369651.7 link	c.1210+832C>T	intron_variant	Intron 6 of 7	2		ENSP00000358665.3	P21589-2
NT5E	ENST00000416334.5 link	c.502+832C>T	intron_variant	Intron 4 of 4	3		ENSP00000414674.1	H0Y7R7
NT5E	ENST00000437581.1 link	c.296-77C>T	intron_variant	Intron 3 of 4	3		ENSP00000387630.1	H0Y3X5

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

2108

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00340

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.0219

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0209

Gnomad OTH

AF:

0.0129

GnomAD4 exome

AF:

0.0175

AC:

24116

AN:

1374946

Hom.:

239

AF XY:

0.0175

AC XY:

12077

AN XY:

689102

show subpopulations

African (AFR)

AF:

0.00277

AC:

AN:

31794

American (AMR)

AF:

0.00673

AC:

300

AN:

44596

Ashkenazi Jewish (ASJ)

AF:

0.0171

AC:

439

AN:

25606

East Asian (EAS)

AF:

0.0000510

AC:

AN:

39200

South Asian (SAS)

AF:

0.00687

AC:

578

AN:

84128

European-Finnish (FIN)

AF:

0.0225

AC:

1141

AN:

50732

Middle Eastern (MID)

AF:

0.0178

AC:

AN:

5512

European-Non Finnish (NFE)

AF:

0.0199

AC:

20609

AN:

1035948

Other (OTH)

AF:

0.0150

AC:

861

AN:

57430

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1281

2562

3844

5125

6406

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

688

1376

2064

2752

3440

<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:

0.0139

AC:

2110

AN:

152334

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1009

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00339

AC:

141

AN:

41582

American (AMR)

AF:

0.0105

AC:

160

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00725

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0219

AC:

233

AN:

10624

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0210

AC:

1426

AN:

68022

Other (OTH)

AF:

0.0128

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

106

213

319

426

532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0151

Hom.:

Bravo

AF:

0.0126

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.11

(source)

DANN

Benign

0.42

PhyloP100

-2.6

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over