12-103793940-T-C

Variant names:

• chr12-103793940-T-C
• rs772178095
• NM_001031701.3:c.811A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031701.3(NT5DC3):​c.811A>G​(p.Ile271Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,457,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NT5DC3 NM_001031701.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.96
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17717159).

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.811A>G	p.Ile271Val	missense	Exon 7 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.811A>G	p.Ile271Val	missense	Exon 7 of 14	ENSP00000376615.3	Q86UY8-1
	NT5DC3	ENST00000933413.1		c.753+2954A>G		intron	N/A	ENSP00000603472.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251414 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457884 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 725662

African (AFR) AF: 0.0000300 AC: 1 AN: 33374

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108420

Other (OTH) AF: 0.00 AC: 0 AN: 60246

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Benign	0.066
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.021
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		6.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.18
Sift	Benign	0.68	T
Sift4G	Benign	0.78	T
Polyphen		0.12	B
Vest4		0.36
MutPred		0.52		Gain of catalytic residue at A266 (P = 0.0192)
MVP		0.13
MPC		0.81
ClinPred		0.46	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.35
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs772178095; hg19: chr12-104187718;