chr12-103798622-C-T

Variant names:

• chr12-103798622-C-T
• rs778333375
• NM_001031701.3:c.580G>A

Variant summary

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

The NM_001031701.3(NT5DC3):​c.580G>A​(p.Val194Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: NT5DC3 NM_001031701.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.73
• 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.580G>A	p.Val194Met	missense	Exon 5 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.580G>A	p.Val194Met	missense	Exon 5 of 14	ENSP00000376615.3	Q86UY8-1
	NT5DC3	ENST00000933413.1		c.580G>A	p.Val194Met	missense	Exon 5 of 10	ENSP00000603472.1
	NT5DC3	ENST00000465502.1	TSL:4	n.378G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251408 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: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461658 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727156

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111808

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

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	0.83
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.7
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.69	P
Vest4		0.72
MutPred		0.54		Gain of catalytic residue at L196 (P = 5e-04)
MVP		0.28
MPC		1.2
ClinPred		0.89	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.37
gMVP		0.78
Mutation Taster		=64/36	polymorphism

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: rs778333375; hg19: chr12-104192400;