NM_001031701.3:c.704T>C

Variant names:

• chr12-103796943-A-G
• NM_001031701.3:c.704T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001031701.3(NT5DC3):​c.704T>C​(p.Leu235Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NT5DC3 NM_001031701.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.92
• 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 2 ACMG points.

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

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.704T>C	p.Leu235Pro	missense	Exon 6 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.704T>C	p.Leu235Pro	missense	Exon 6 of 14	ENSP00000376615.3	Q86UY8-1
	NT5DC3	ENST00000933413.1		c.704T>C	p.Leu235Pro	missense	Exon 6 of 10	ENSP00000603472.1
	NT5DC3	ENST00000465502.1	TSL:4	n.502T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.97
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		8.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.29
Sift	Benign	0.28	T
Sift4G	Benign	0.30	T
Polyphen		0.98	D
Vest4		0.60
MutPred		0.57		Loss of stability (P = 0.0059)
MVP		0.47
MPC		1.7
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.81
gMVP		0.83
Mutation Taster		=17/83	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

hg19: chr12-104190721;