rs2229524

chr6-85489525-T-Achr6-85489525-T-Cchr6-85489525-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002526.4(NT5E):c.1136T>A(p.Met379Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M379T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NT5E NM_002526.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.682

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035946786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5E	NM_002526.4	c.1136T>A	p.Met379Lys	missense_variant	6/9	ENST00000257770.8
NT5E	NM_001204813.2	c.1136T>A	p.Met379Lys	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5E	ENST00000257770.8	c.1136T>A	p.Met379Lys	missense_variant	6/9	1	NM_002526.4	P1
NT5E	ENST00000369651.7	c.1136T>A	p.Met379Lys	missense_variant	6/8	2
NT5E	ENST00000416334.5	c.431T>A	p.Met144Lys	missense_variant	4/5	3
NT5E	ENST00000437581.1	c.224T>A	p.Met75Lys	missense_variant	3/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	10
Dann	Benign	0.61
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.94	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.75	N;N
REVEL	Benign	0.12
Sift	Benign	0.94	T;T
Sift4G	Benign	0.93	T;T
Polyphen		0.0	.;B
Vest4		0.21
MutPred		0.55		Gain of methylation at M379 (P = 0.0135);Gain of methylation at M379 (P = 0.0135);
MVP		0.20
MPC		0.27
ClinPred		0.040	T
GERP RS		-0.33
Varity_R		0.17
gMVP		0.79

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: rs2229524; hg19: chr6-86199243;