rs3753603

Positions:

• chr1-32621836-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178547.5(ZBTB8OS):​c.*26C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0582 in 1,484,284 control chromosomes in the GnomAD database, including 6,564 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 0.14 (2900 hom., cov: 32)
  • Exomes 𝑓: 0.049 (3664 hom.)
• Consequence: ZBTB8OS NM_178547.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120

Genes affected

ZBTB8OS (HGNC:24094): (zinc finger and BTB domain containing 8 opposite strand) Predicted to enable metal ion binding activity. Involved in tRNA splicing, via endonucleolytic cleavage and ligation. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB8OS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZBTB8OS	NM_178547.5	c.*26C>T		3_prime_UTR_variant	7/7	ENST00000468695.6	NP_848642.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZBTB8OS	ENST00000468695.6	c.*26C>T		3_prime_UTR_variant	7/7	1	NM_178547.5	ENSP00000417677.2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20674 AN: 151822 Hom.: 2896 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0596

Gnomad FIN AF: 0.0217

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.133

GnomAD3 exomes AF: 0.0759 AC: 16587 AN: 218412 Hom.: 1454 AF XY: 0.0673 AC XY: 8007 AN XY: 118982

Gnomad AFR exome AF: 0.351

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.0362

Gnomad EAS exome AF: 0.119

Gnomad SAS exome AF: 0.0546

Gnomad FIN exome AF: 0.0209

Gnomad NFE exome AF: 0.0357

Gnomad OTH exome AF: 0.0595

GnomAD4 exome AF: 0.0493 AC: 65672 AN: 1332344 Hom.: 3664 Cov.: 20 AF XY: 0.0484 AC XY: 32337 AN XY: 667962

Gnomad4 AFR exome AF: 0.362

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.0391

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.0546

Gnomad4 FIN exome AF: 0.0212

Gnomad4 NFE exome AF: 0.0350

Gnomad4 OTH exome AF: 0.0689

GnomAD4 genome AF: 0.136 AC: 20716 AN: 151940 Hom.: 2900 Cov.: 32 AF XY: 0.135 AC XY: 10043 AN XY: 74252

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.0383

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.0594

Gnomad4 FIN AF: 0.0217

Gnomad4 NFE AF: 0.0361

Gnomad4 OTH AF: 0.132

Alfa AF: 0.0785 Hom.: 324

Bravo AF: 0.159

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs3753603; hg19: chr1-33087437; COSMIC: COSV59384734; COSMIC: COSV59384734;