6-116117866-C-A

Variant names:

• chr6-116117866-C-A
• rs757159964
• NM_152729.3:c.450C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.423
• Publications: 0 publications found

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]

ACMG classification

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	c.450C>A	p.Asn150Lys	missense_variant	Exon 6 of 12	ENST00000319550.9	NP_689942.2
NT5DC1	XM_006715378.4	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	Appris	UniProt
NT5DC1	ENST00000319550.9	c.450C>A	p.Asn150Lys	missense_variant	Exon 6 of 12	1	NM_152729.3	ENSP00000326858.3
NT5DC1	ENST00000419791.3	c.450C>A	p.Asn150Lys	missense_variant	Exon 6 of 7	3		ENSP00000393578.1
NT5DC1	ENST00000417846.2	n.191C>A		non_coding_transcript_exon_variant	Exon 3 of 3	3
NT5DC1	ENST00000460749.1	n.-55C>A		upstream_gene_variant		5		ENSP00000433238.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152044 Hom.: 0 Cov.: 33

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: 8 AN: 243516 AF XY: 0.0000228

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: 53 AN: 1387676 Hom.: 0 Cov.: 23 AF XY: 0.0000288 AC XY: 20 AN XY: 693812

African (AFR) AF: 0.0000315 AC: 1 AN: 31794

American (AMR) AF: 0.00 AC: 0 AN: 42688

Ashkenazi Jewish (ASJ) AF: 0.0000392 AC: 1 AN: 25534

East Asian (EAS) AF: 0.00 AC: 0 AN: 39162

South Asian (SAS) AF: 0.00 AC: 0 AN: 82202

European-Finnish (FIN) AF: 0.000244 AC: 13 AN: 53278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5418

European-Non Finnish (NFE) AF: 0.0000352 AC: 37 AN: 1049740

Other (OTH) AF: 0.0000173 AC: 1 AN: 57860

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152044 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74260

African (AFR) AF: 0.0000242 AC: 1 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000412 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.80
DEOGEN2	Benign	0.010	T;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L;.
PhyloP100		-0.42
PrimateAI	Uncertain	0.51	T
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	T
GERP RS		0.61
Varity_R		0.062
gMVP		0.27
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs757159964; hg19: chr6-116439029;