Variant 3-52527646-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001134231.2(NT5DC2):c.1008C>G(p.Asp336Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NT5DC2
NM_001134231.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.374

Variant links:

Genes affected

NT5DC2 (HGNC:25717): (5'-nucleotidase domain containing 2) Predicted to enable 5'-nucleotidase activity. Predicted to be involved in dephosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

NT5DC2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34529597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5DC2	NM_001134231.2 link	c.1008C>G	p.Asp336Glu	missense_variant	9/14	ENST00000422318.7	NP_001127703.1	Q9H857-2
NT5DC2	NM_022908.3 link	c.897C>G	p.Asp299Glu	missense_variant	9/14		NP_075059.1	Q9H857-1
NT5DC2	XM_006713303.4 link	c.1008C>G	p.Asp336Glu	missense_variant	9/14		XP_006713366.1
NT5DC2	XM_047448760.1 link	c.897C>G	p.Asp299Glu	missense_variant	9/14		XP_047304716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5DC2	ENST00000422318.7 link	c.1008C>G	p.Asp336Glu	missense_variant	9/14	5	NM_001134231.2	ENSP00000406933.2		Q9H857-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460786

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726688

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 22, 2024

The c.1008C>G (p.D336E) alteration is located in exon 9 (coding exon 9) of the NT5DC2 gene. This alteration results from a C to G substitution at nucleotide position 1008, causing the aspartic acid (D) at amino acid position 336 to be replaced by a glutamic acid (E). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0075

T;T;.;.

Eigen

Benign

-0.014

Eigen_PC

Benign

0.0013

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.77

T;T;T;T

M_CAP

Benign

0.0099

MetaRNN

Benign

0.35

T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.1

.;M;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.28

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.90

T;T;T;T

Sift4G

Benign

0.54

T;T;T;T

Polyphen

0.020

.;B;.;.

Vest4

0.42, 0.41, 0.42

MutPred

0.32

.;Loss of ubiquitination at K300 (P = 0.1601);.;.;

MVP

0.35

MPC

0.36

ClinPred

0.18

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.099

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over