17-41830878-T-C

Variant names:

• chr17-41830878-T-C
• rs4796712
• NM_052935.5:c.327A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_052935.5(NT5C3B):​c.327A>G​(p.Ala109Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 1,602,722 control chromosomes in the GnomAD database, including 661,584 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.90 (61278 hom., cov: 31)
  • Exomes 𝑓: 0.91 (600306 hom.)
• Consequence: NT5C3B NM_052935.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.63
• Publications: 35 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP7: Synonymous conserved (PhyloP=-3.63 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052935.5. 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
	NT5C3B	NM_052935.5	MANE Select	c.327A>G	p.Ala109Ala	synonymous	Exon 6 of 9	NP_443167.4
	NT5C3B	NR_033464.2		n.469A>G		non_coding_transcript_exon	Exon 6 of 9
	NT5C3B	NR_033465.2		n.590A>G		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C3B	ENST00000435506.7	TSL:5 MANE Select	c.327A>G	p.Ala109Ala	synonymous	Exon 6 of 9	ENSP00000389948.2	Q969T7-1
	NT5C3B	ENST00000523903.5	TSL:1	n.616A>G		non_coding_transcript_exon	Exon 5 of 8
	NT5C3B	ENST00000946251.1		c.327A>G	p.Ala109Ala	synonymous	Exon 6 of 10	ENSP00000616310.1

Frequencies

GnomAD3 genomes AF: 0.896 AC: 136285 AN: 152050 Hom.: 61228 Cov.: 31

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.926

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.896

GnomAD2 exomes AF: 0.918 AC: 226652 AN: 246970 AF XY: 0.918

Gnomad AFR exome AF: 0.851

Gnomad AMR exome AF: 0.942

Gnomad ASJ exome AF: 0.926

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.878

Gnomad NFE exome AF: 0.907

Gnomad OTH exome AF: 0.914

GnomAD4 exome AF: 0.909 AC: 1319092 AN: 1450554 Hom.: 600306 Cov.: 31 AF XY: 0.910 AC XY: 657525 AN XY: 722360

African (AFR) AF: 0.847 AC: 27718 AN: 32736

American (AMR) AF: 0.940 AC: 40206 AN: 42782

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 24049 AN: 25992

East Asian (EAS) AF: 1.00 AC: 39602 AN: 39606

South Asian (SAS) AF: 0.942 AC: 80557 AN: 85522

European-Finnish (FIN) AF: 0.883 AC: 47116 AN: 53350

Middle Eastern (MID) AF: 0.861 AC: 4954 AN: 5754

European-Non Finnish (NFE) AF: 0.905 AC: 1000419 AN: 1104876

Other (OTH) AF: 0.909 AC: 54471 AN: 59936

GnomAD4 genome AF: 0.896 AC: 136392 AN: 152168 Hom.: 61278 Cov.: 31 AF XY: 0.897 AC XY: 66712 AN XY: 74404

African (AFR) AF: 0.855 AC: 35494 AN: 41510

American (AMR) AF: 0.926 AC: 14142 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3209 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5160 AN: 5162

South Asian (SAS) AF: 0.949 AC: 4564 AN: 4808

European-Finnish (FIN) AF: 0.870 AC: 9223 AN: 10604

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61612 AN: 68022

Other (OTH) AF: 0.898 AC: 1901 AN: 2116

Alfa AF: 0.902 Hom.: 96295

Bravo AF: 0.898

Asia WGS AF: 0.973 AC: 3385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.57
PhyloP100		-3.6
PromoterAI		-0.0078	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs4796712; hg19: chr17-39987130; COSMIC: COSV108070654; COSMIC: COSV108070654;