NM_001031701.3:c.991A>C

Variant names:

• chr12-103793192-T-G
• NM_001031701.3:c.991A>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001031701.3(NT5DC3):​c.991A>C​(p.Lys331Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,814 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: NT5DC3 NM_001031701.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

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.991A>C	p.Lys331Gln	missense	Exon 9 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.991A>C	p.Lys331Gln	missense	Exon 9 of 14	ENSP00000376615.3	Q86UY8-1
	NT5DC3	ENST00000933413.1		c.753+3702A>C		intron	N/A	ENSP00000603472.1
	NT5DC3	ENST00000415849.1	TSL:5	n.136A>C		non_coding_transcript_exon	Exon 2 of 8	ENSP00000399171.1	H7C193

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453814 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722916

African (AFR) AF: 0.00 AC: 0 AN: 32926

American (AMR) AF: 0.00 AC: 0 AN: 41966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 83878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110160

Other (OTH) AF: 0.0000166 AC: 1 AN: 60128

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	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.071	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.063	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		8.0
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.71		Loss of methylation at K331 (P = 0.0014)
MVP		0.85
MPC		1.4
ClinPred		0.99	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.98
Mutation Taster		=27/73	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: chr12-104186970;