rs1046403

Variant names:

• chr17-41827568-G-A
• rs1046403
• NM_052935.5:c.626C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052935.5(NT5C3B):​c.626C>T​(p.Ala209Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 860,298 control chromosomes in the GnomAD database, including 255,593 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.76 (44595 hom., cov: 32)
  • Exomes 𝑓: 0.77 (210998 hom.)
• Consequence: NT5C3B NM_052935.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 46 publications found

Genes affected

NT5C3B (HGNC:28300): (5'-nucleotidase, cytosolic IIIB) Predicted to enable 5'-nucleotidase activity. Predicted to be involved in exonucleolytic catabolism of deadenylated mRNA. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.7349597E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C3B	NM_052935.5	c.626C>T	p.Ala209Val	missense_variant	Exon 8 of 9	ENST00000435506.7	NP_443167.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C3B	ENST00000435506.7	c.626C>T	p.Ala209Val	missense_variant	Exon 8 of 9	5	NM_052935.5	ENSP00000389948.2

Frequencies

GnomAD3 genomes AF: 0.763 AC: 116047 AN: 152028 Hom.: 44558 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.772

GnomAD2 exomes AF: 0.778 AC: 195605 AN: 251400 AF XY: 0.777

Gnomad AFR exome AF: 0.767

Gnomad AMR exome AF: 0.884

Gnomad ASJ exome AF: 0.859

Gnomad EAS exome AF: 0.825

Gnomad FIN exome AF: 0.637

Gnomad NFE exome AF: 0.751

Gnomad OTH exome AF: 0.785

GnomAD4 exome AF: 0.768 AC: 543863 AN: 708152 Hom.: 210998 Cov.: 0 AF XY: 0.771 AC XY: 292093 AN XY: 379006

African (AFR) AF: 0.770 AC: 15154 AN: 19684

American (AMR) AF: 0.880 AC: 38599 AN: 43868

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 18310 AN: 21432

East Asian (EAS) AF: 0.844 AC: 30779 AN: 36456

South Asian (SAS) AF: 0.811 AC: 57964 AN: 71454

European-Finnish (FIN) AF: 0.650 AC: 34526 AN: 53140

Middle Eastern (MID) AF: 0.795 AC: 3419 AN: 4302

European-Non Finnish (NFE) AF: 0.753 AC: 317840 AN: 422194

Other (OTH) AF: 0.766 AC: 27272 AN: 35622

GnomAD4 genome AF: 0.763 AC: 116135 AN: 152146 Hom.: 44595 Cov.: 32 AF XY: 0.762 AC XY: 56613 AN XY: 74344

African (AFR) AF: 0.767 AC: 31819 AN: 41504

American (AMR) AF: 0.844 AC: 12917 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2967 AN: 3470

East Asian (EAS) AF: 0.827 AC: 4277 AN: 5170

South Asian (SAS) AF: 0.810 AC: 3909 AN: 4826

European-Finnish (FIN) AF: 0.626 AC: 6620 AN: 10570

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 51018 AN: 67990

Other (OTH) AF: 0.772 AC: 1631 AN: 2112

Alfa AF: 0.762 Hom.: 125299

Bravo AF: 0.781

TwinsUK AF: 0.746 AC: 2766

ALSPAC AF: 0.744 AC: 2869

ESP6500AA AF: 0.761 AC: 3354

ESP6500EA AF: 0.760 AC: 6538

ExAC AF: 0.777 AC: 94334

Asia WGS AF: 0.820 AC: 2852 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	12
DANN	Benign	0.80
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.40	T;T
MetaRNN	Benign	0.0000017	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.48	N;.
PhyloP100		2.5
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.51	N;N
REVEL	Benign	0.29
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;.
Vest4		0.026
MPC		0.12
ClinPred		0.00091	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.029
gMVP		0.45
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1046403; hg19: chr17-39983820; COSMIC: COSV54056904; COSMIC: COSV54056904;