rs35694460

chr6-85467062-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_002526.4(NT5E):c.342A>G(p.Ala114=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 1,613,664 control chromosomes in the GnomAD database, including 179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (100 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (79 hom.)
• Consequence: NT5E NM_002526.4 splice_region, synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.595

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 6-85467062-A-G is Benign according to our data. Variant chr6-85467062-A-G is described in ClinVar as [Benign]. Clinvar id is 783471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.595 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5E	NM_002526.4	c.342A>G	p.Ala114=	splice_region_variant, synonymous_variant	2/9	ENST00000257770.8
NT5E	NM_001204813.2	c.342A>G	p.Ala114=	splice_region_variant, synonymous_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5E	ENST00000257770.8	c.342A>G	p.Ala114=	splice_region_variant, synonymous_variant	2/9	1	NM_002526.4	P1
NT5E	ENST00000369646.7	c.342A>G	p.Ala114=	splice_region_variant, synonymous_variant	2/3	1
NT5E	ENST00000369651.7	c.342A>G	p.Ala114=	splice_region_variant, synonymous_variant	2/8	2

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2852 AN: 152104 Hom.: 100 Cov.: 32

Gnomad AFR AF: 0.0653

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00497 AC: 1248 AN: 251190 Hom.: 42 AF XY: 0.00348 AC XY: 473 AN XY: 135768

Gnomad AFR exome AF: 0.0685

Gnomad AMR exome AF: 0.00330

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00188 AC: 2754 AN: 1461442 Hom.: 79 Cov.: 32 AF XY: 0.00157 AC XY: 1143 AN XY: 727068

Gnomad4 AFR exome AF: 0.0671

Gnomad4 AMR exome AF: 0.00387

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000162

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000495

Gnomad4 OTH exome AF: 0.00414

GnomAD4 genome AF: 0.0187 AC: 2853 AN: 152222 Hom.: 100 Cov.: 32 AF XY: 0.0184 AC XY: 1369 AN XY: 74406

Gnomad4 AFR AF: 0.0651

Gnomad4 AMR AF: 0.00700

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00908 Hom.: 17

Bravo AF: 0.0217

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	11
Dann	Benign	0.64

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: rs35694460; hg19: chr6-86176780;