NM_001031701.3:c.1505C>A

Variant names:

• chr12-103777971-G-T
• rs1020141660
• NM_001031701.3:c.1505C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001031701.3(NT5DC3):​c.1505C>A​(p.Ala502Glu) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A502V) has been classified 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: 7.62
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38715106).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031701.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5DC3	NM_001031701.3	MANE Select	c.1505C>A	p.Ala502Glu	missense	Exon 14 of 14	NP_001026871.1	Q86UY8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5DC3	ENST00000392876.8	TSL:1 MANE Select	c.1505C>A	p.Ala502Glu	missense	Exon 14 of 14	ENSP00000376615.3	Q86UY8-1
	NT5DC3	ENST00000933413.1		c.1157C>A	p.Ala386Glu	missense	Exon 10 of 10	ENSP00000603472.1
	NT5DC3	ENST00000447799.5	TSL:2	n.224C>A		non_coding_transcript_exon	Exon 3 of 5	ENSP00000413657.1	H7C3S8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.29
Sift	Benign	0.051	T
Sift4G	Uncertain	0.041	D
Polyphen		0.37	B
Vest4		0.56
MutPred		0.66		Gain of catalytic residue at I499 (P = 9e-04)
MVP		0.48
MPC		1.1
ClinPred		0.97	D
GERP RS		4.9
Varity_R		0.46
gMVP		0.94
Mutation Taster		=31/69	disease causing

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: rs1020141660; hg19: chr12-104171749;