rs10944129

Variant names:

• chr6-85471208-A-G
• rs10944129
• NM_002526.4:c.563-29A>G

Variant summary

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

The NM_002526.4(NT5E):​c.563-29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,451,506 control chromosomes in the GnomAD database, including 205,954 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 0.47 (18086 hom., cov: 33)
  • Exomes 𝑓: 0.53 (187868 hom.)
• Consequence: NT5E NM_002526.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• 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=-0.66).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5E	NM_002526.4	c.563-29A>G		intron_variant	Intron 2 of 8	ENST00000257770.8	NP_002517.1
NT5E	NM_001204813.2	c.563-29A>G		intron_variant	Intron 2 of 7		NP_001191742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5E	ENST00000257770.8	c.563-29A>G		intron_variant	Intron 2 of 8	1	NM_002526.4	ENSP00000257770.3
NT5E	ENST00000369646.7	c.563-29A>G		intron_variant	Intron 2 of 2	1		ENSP00000358660.3
NT5E	ENST00000369651.7	c.563-29A>G		intron_variant	Intron 2 of 7	2		ENSP00000358665.3
NT5E	ENST00000416334.5	c.-175A>G		upstream_gene_variant		3		ENSP00000414674.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72016 AN: 151926 Hom.: 18064 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.487

GnomAD2 exomes AF: 0.536 AC: 105654 AN: 197208 AF XY: 0.536

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.663

Gnomad ASJ exome AF: 0.558

Gnomad EAS exome AF: 0.340

Gnomad FIN exome AF: 0.518

Gnomad NFE exome AF: 0.550

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.534 AC: 693707 AN: 1299460 Hom.: 187868 Cov.: 18 AF XY: 0.533 AC XY: 346354 AN XY: 649488

African (AFR) AF: 0.297 AC: 8608 AN: 29020

American (AMR) AF: 0.656 AC: 26851 AN: 40944

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 13722 AN: 24706

East Asian (EAS) AF: 0.318 AC: 11292 AN: 35458

South Asian (SAS) AF: 0.545 AC: 41058 AN: 75292

European-Finnish (FIN) AF: 0.516 AC: 25841 AN: 50076

Middle Eastern (MID) AF: 0.549 AC: 2921 AN: 5316

European-Non Finnish (NFE) AF: 0.543 AC: 534950 AN: 984332

Other (OTH) AF: 0.524 AC: 28464 AN: 54316

GnomAD4 genome AF: 0.474 AC: 72075 AN: 152046 Hom.: 18086 Cov.: 33 AF XY: 0.476 AC XY: 35355 AN XY: 74338

African (AFR) AF: 0.306 AC: 12693 AN: 41480

American (AMR) AF: 0.589 AC: 8997 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1906 AN: 3472

East Asian (EAS) AF: 0.335 AC: 1736 AN: 5184

South Asian (SAS) AF: 0.526 AC: 2529 AN: 4808

European-Finnish (FIN) AF: 0.520 AC: 5473 AN: 10534

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36924 AN: 67984

Other (OTH) AF: 0.492 AC: 1040 AN: 2112

Alfa AF: 0.528 Hom.: 9626

Bravo AF: 0.475

Asia WGS AF: 0.446 AC: 1545 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	10
DANN	Benign	0.91
PhyloP100		1.0
PromoterAI		0.024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10944129; hg19: chr6-86180926;