6-85467183-T-A

Position:

• chr6-85467183-T-A

Variant summary

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

The NM_002526.4(NT5E):​c.463T>A​(p.Ser155Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NT5E NM_002526.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0590

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=0.07820994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5E	NM_002526.4	c.463T>A	p.Ser155Thr	missense_variant	2/9	ENST00000257770.8	NP_002517.1
NT5E	NM_001204813.2	c.463T>A	p.Ser155Thr	missense_variant	2/8		NP_001191742.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5E	ENST00000257770.8	c.463T>A	p.Ser155Thr	missense_variant	2/9	1	NM_002526.4	ENSP00000257770	P1
NT5E	ENST00000369646.7	c.463T>A	p.Ser155Thr	missense_variant	2/3	1		ENSP00000358660
NT5E	ENST00000369651.7	c.463T>A	p.Ser155Thr	missense_variant	2/8	2		ENSP00000358665

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461840 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2022

The c.463T>A (p.S155T) alteration is located in exon 2 (coding exon 2) of the NT5E gene. This alteration results from a T to A substitution at nucleotide position 463, causing the serine (S) at amino acid position 155 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.92
DEOGEN2	Benign	0.41	.;.;T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.078	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.61	N;.;N
MutationTaster	Benign	0.51	D;D;D
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.022
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.58	T;T;T
Polyphen		0.0090, 0.0050	.;B;B
Vest4		0.26
MutPred		0.34		Loss of glycosylation at S155 (P = 0.0549);Loss of glycosylation at S155 (P = 0.0549);Loss of glycosylation at S155 (P = 0.0549);
MVP		0.35
MPC		0.16
ClinPred		0.096	T
GERP RS		3.0
Varity_R		0.25
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-86176901;