rs35478984

Positions:

• chr6-85485380-C-A
• chr6-85485380-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002526.4(NT5E):​c.897C>A​(p.Asn299Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NT5E NM_002526.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.172436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5E	NM_002526.4	c.897C>A	p.Asn299Lys	missense_variant	4/9	ENST00000257770.8	NP_002517.1
NT5E	NM_001204813.2	c.897C>A	p.Asn299Lys	missense_variant	4/8		NP_001191742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5E	ENST00000257770.8	c.897C>A	p.Asn299Lys	missense_variant	4/9	1	NM_002526.4	ENSP00000257770.3
NT5E	ENST00000369651.7	c.897C>A	p.Asn299Lys	missense_variant	4/8	2		ENSP00000358665.3
NT5E	ENST00000416334.5	c.189C>A	p.Asn63Lys	missense_variant	2/5	3		ENSP00000414674.1
NT5E	ENST00000437581.1	c.-19C>A		upstream_gene_variant		3		ENSP00000387630.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461864 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.1
DANN	Benign	0.90
DEOGEN2	Benign	0.29	.;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.073
Sift	Benign	0.37	T;T
Sift4G	Benign	0.61	T;T
Polyphen		0.024	.;B
Vest4		0.25
MutPred		0.39		Gain of ubiquitination at N299 (P = 0.0267);Gain of ubiquitination at N299 (P = 0.0267);
MVP		0.41
MPC		0.20
ClinPred		0.25	T
GERP RS		-0.10
Varity_R		0.23
gMVP		0.66

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: rs35478984; hg19: chr6-86195098;