Genetic Variant NM_152729.3:c.450C>A (chr6-116117866-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152729.3(NT5DC1):c.450C>A(p.Asn150Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,539,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

NT5DC1
NM_152729.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.423

Publications

0 publications found

Variant links:

Genes affected

NT5DC1 (HGNC:21556): (5'-nucleotidase domain containing 1) While the exact function of the protein encoded by this gene is not known, it belongs to the 5'(3')-deoxyribonucleotidase family. [provided by RefSeq, May 2010]

NT5DC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08748788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5DC1	NM_152729.3 link	c.450C>A	p.Asn150Lys	missense_variant	Exon 6 of 12	ENST00000319550.9	NP_689942.2	Q5TFE4-1Q9H2R1
NT5DC1	XM_006715378.4 link	c.450C>A	p.Asn150Lys	missense_variant	Exon 6 of 10		XP_006715441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NT5DC1	ENST00000319550.9 link	c.450C>A	p.Asn150Lys	missense_variant	Exon 6 of 12	1	NM_152729.3	ENSP00000326858.3	Q5TFE4-1
NT5DC1	ENST00000419791.3 link	c.450C>A	p.Asn150Lys	missense_variant	Exon 6 of 7	3		ENSP00000393578.1	Q5QPD0
NT5DC1	ENST00000417846.2 link	n.191C>A		non_coding_transcript_exon_variant	Exon 3 of 3	3
NT5DC1	ENST00000460749.1 link	n.-55C>A		upstream_gene_variant		5		ENSP00000433238.1	H0YDA5

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000329

AC:

AN:

243516

AF XY:

0.0000228

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000382

AC:

AN:

1387676

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

693812

show subpopulations

African (AFR)

AF:

0.0000315

AC:

AN:

31794

American (AMR)

AF:

0.00

AC:

AN:

42688

Ashkenazi Jewish (ASJ)

AF:

0.0000392

AC:

AN:

25534

East Asian (EAS)

AF:

0.00

AC:

AN:

39162

South Asian (SAS)

AF:

0.00

AC:

AN:

82202

European-Finnish (FIN)

AF:

0.000244

AC:

AN:

53278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5418

European-Non Finnish (NFE)

AF:

0.0000352

AC:

AN:

1049740

Other (OTH)

AF:

0.0000173

AC:

AN:

57860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152044

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 05, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.450C>A (p.N150K) alteration is located in exon 6 (coding exon 6) of the NT5DC1 gene. This alteration results from a C to A substitution at nucleotide position 450, causing the asparagine (N) at amino acid position 150 to be replaced by a lysine (K). 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

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.010

T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.56

T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.087

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

L;.

PhyloP100

-0.42

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.59

N;N

REVEL

Benign

0.065

Sift

Benign

0.50

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.015

B;.

Vest4

0.15

MutPred

0.63

Gain of methylation at N150 (P = 0.016);Gain of methylation at N150 (P = 0.016);

MVP

0.26

MPC

0.14

ClinPred

0.053

GERP RS

0.61

Varity_R

0.062

gMVP

0.27

Mutation Taster

=91/9

polymorphism

(source)

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

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NM_152729.3:c.450C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over