3-52524994-T-G

Position:

• chr3-52524994-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001134231.2(NT5DC2):​c.1316A>C​(p.Gln439Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NT5DC2 NM_001134231.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.97

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.901

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NT5DC2	NM_001134231.2	c.1316A>C	p.Gln439Pro	missense_variant	12/14	ENST00000422318.7
NT5DC2	NM_022908.3	c.1205A>C	p.Gln402Pro	missense_variant	12/14
NT5DC2	XM_006713303.4	c.1316A>C	p.Gln439Pro	missense_variant	12/14
NT5DC2	XM_047448760.1	c.1205A>C	p.Gln402Pro	missense_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NT5DC2	ENST00000422318.7	c.1316A>C	p.Gln439Pro	missense_variant	12/14	5	NM_001134231.2	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 58

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 22, 2024

The c.1316A>C (p.Q439P) alteration is located in exon 12 (coding exon 12) of the NT5DC2 gene. This alteration results from a A to C substitution at nucleotide position 1316, causing the glutamine (Q) at amino acid position 439 to be replaced by a proline (P). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;T;.;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.90	D;D;D;D
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	3.3	.;M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-4.9	D;D;D;D
REVEL	Uncertain	0.59
Sift	Benign	0.037	D;D;D;D
Sift4G	Uncertain	0.029	D;T;D;D
Polyphen		0.92	.;P;.;.
Vest4		0.96, 0.95, 0.94
MutPred		0.76		.;Loss of MoRF binding (P = 0.1124);.;.;
MVP		0.41
MPC		1.2
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.87
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr3-52559010;