rs10944129

Positions:

• chr6-85471208-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NT5E	NM_002526.4	c.563-29A>G		intron_variant		ENST00000257770.8	NP_002517.1
NT5E	NM_001204813.2	c.563-29A>G		intron_variant			NP_001191742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5E	ENST00000257770.8	c.563-29A>G		intron_variant		1	NM_002526.4	ENSP00000257770	P1
NT5E	ENST00000369646.7	c.563-29A>G		intron_variant		1		ENSP00000358660
NT5E	ENST00000369651.7	c.563-29A>G		intron_variant		2		ENSP00000358665

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

GnomAD3 exomes AF: 0.536 AC: 105654 AN: 197208 Hom.: 29168 AF XY: 0.536 AC XY: 57292 AN XY: 106856

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 SAS exome AF: 0.543

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

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.656

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.318

Gnomad4 SAS exome AF: 0.545

Gnomad4 FIN exome AF: 0.516

Gnomad4 NFE exome AF: 0.543

Gnomad4 OTH exome AF: 0.524

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

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.492

Alfa AF: 0.529 Hom.: 7896

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

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

LitVar

Other links and lift over

dbSNP: rs10944129; hg19: chr6-86180926;