chr17-41830813-T-A

Variant names:

• chr17-41830813-T-A
• rs782344608
• NM_052935.5:c.392A>T

Variant summary

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

The NM_052935.5(NT5C3B):​c.392A>T​(p.Asn131Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N131S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NT5C3B NM_052935.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.728
• Publications: 0 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: 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=0.1969957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C3B	NM_052935.5	c.392A>T	p.Asn131Ile	missense_variant	Exon 6 of 9	ENST00000435506.7	NP_443167.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C3B	ENST00000435506.7	c.392A>T	p.Asn131Ile	missense_variant	Exon 6 of 9	5	NM_052935.5	ENSP00000389948.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.79
DEOGEN2	Uncertain	0.69	D;D;D
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.49	N
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.1	.;L;.
PhyloP100		0.73
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-4.9	D;D;.
REVEL	Benign	0.17
Sift	Benign	0.11	T;D;.
Sift4G	Benign	0.12	T;T;T
Polyphen		0.91	P;.;.
Vest4		0.47
MVP		0.25
MPC		0.20
ClinPred		0.58	D
GERP RS		-1.7
PromoterAI		0.0056	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.60

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: rs782344608; hg19: chr17-39987065;