3-52525240-T-G

Position:

• chr3-52525240-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001134231.2(NT5DC2):​c.1175A>C​(p.Tyr392Ser) 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: 8.01

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5DC2	NM_001134231.2	c.1175A>C	p.Tyr392Ser	missense_variant	11/14	ENST00000422318.7	NP_001127703.1
NT5DC2	NM_022908.3	c.1064A>C	p.Tyr355Ser	missense_variant	11/14		NP_075059.1
NT5DC2	XM_006713303.4	c.1175A>C	p.Tyr392Ser	missense_variant	11/14		XP_006713366.1
NT5DC2	XM_047448760.1	c.1064A>C	p.Tyr355Ser	missense_variant	11/14		XP_047304716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5DC2	ENST00000422318.7	c.1175A>C	p.Tyr392Ser	missense_variant	11/14	5	NM_001134231.2	ENSP00000406933.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Nov 27, 2024

The c.1175A>C (p.Y392S) alteration is located in exon 11 (coding exon 11) of the NT5DC2 gene. This alteration results from a A to C substitution at nucleotide position 1175, causing the tyrosine (Y) at amino acid position 392 to be replaced by a serine (S). 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	0.99
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;T;.;.
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	1.0	D;D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.98	D;D;D;D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Pathogenic	3.6	.;H;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-8.7	D;D;D;D
REVEL	Pathogenic	0.85
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.99, 0.98
MutPred		0.92		.;Loss of stability (P = 0.0365);.;.;
MVP		0.91
MPC		1.3
ClinPred		1.0	D
GERP RS		5.1
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.8
Varity_R		0.96
gMVP		0.97

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: chr3-52559256;