rs9450279

Variant names:

• chr6-85449506-C-T
• rs9450279
• ENST00000369651.7:c.-634C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369651.7(NT5E):​c.-634C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,122 control chromosomes in the GnomAD database, including 3,360 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 0.19 (3360 hom., cov: 32)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: NT5E ENST00000369651.7 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 8 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5E	ENST00000369651.7	c.-634C>T		upstream_gene_variant		2		ENSP00000358665.3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29062 AN: 151962 Hom.: 3359 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0619

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.0714 AC: 3 AN: 42 Hom.: 0 AF XY: 0.0909 AC XY: 2 AN XY: 22

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0667 AC: 2 AN: 30

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.191 AC: 29088 AN: 152080 Hom.: 3360 Cov.: 32 AF XY: 0.186 AC XY: 13825 AN XY: 74344

African (AFR) AF: 0.328 AC: 13585 AN: 41438

American (AMR) AF: 0.134 AC: 2044 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 556 AN: 3468

East Asian (EAS) AF: 0.0618 AC: 320 AN: 5174

South Asian (SAS) AF: 0.167 AC: 806 AN: 4818

European-Finnish (FIN) AF: 0.106 AC: 1121 AN: 10600

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.149 AC: 10110 AN: 67988

Other (OTH) AF: 0.169 AC: 357 AN: 2112

Alfa AF: 0.169 Hom.: 524

Bravo AF: 0.198

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.015
DANN	Benign	0.87
PhyloP100		-1.3
PromoterAI		-0.38	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9450279; hg19: chr6-86159224;