12-103777957-G-A

Position:

• chr12-103777957-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001031701.3(NT5DC3):​c.1519C>T​(p.Leu507Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NT5DC3 NM_001031701.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.33

Genes affected

NT5DC3 (HGNC:30826): (5'-nucleotidase domain containing 3) Predicted to enable 5'-nucleotidase activity. Predicted to be involved in dephosphorylation. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

NT5DC3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5DC3	NM_001031701.3	c.1519C>T	p.Leu507Phe	missense_variant	14/14	ENST00000392876.8	NP_001026871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5DC3	ENST00000392876.8	c.1519C>T	p.Leu507Phe	missense_variant	14/14	1	NM_001031701.3	ENSP00000376615.3
NT5DC3	ENST00000447799.5	n.238C>T		non_coding_transcript_exon_variant	3/5	2		ENSP00000413657.1
NT5DC3	ENST00000415849.1	n.*436C>T		downstream_gene_variant		5		ENSP00000399171.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Jun 29, 2023

The c.1519C>T (p.L507F) alteration is located in exon 14 (coding exon 14) of the NT5DC3 gene. This alteration results from a C to T substitution at nucleotide position 1519, causing the leucine (L) at amino acid position 507 to be replaced by a phenylalanine (F). 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	0.36
BayesDel_addAF	Benign	-0.0017	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.23
Sift	Benign	0.12	T
Sift4G	Benign	0.19	T
Polyphen		0.68	P
Vest4		0.59
MutPred		0.73		Gain of catalytic residue at D511 (P = 0.0037);
MVP		0.66
MPC		1.4
ClinPred		0.87	D
GERP RS		5.8
Varity_R		0.29
gMVP		0.80

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: chr12-104171735;