rs3753603

Variant names:

• chr1-32621836-G-A
• rs3753603
• NM_178547.5:c.*26C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178547.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB8OS	NM_178547.5	MANE Select	c.*26C>T		3_prime_UTR	Exon 7 of 7	NP_848642.2
	ZBTB8OS	NR_158772.1		n.984C>T		non_coding_transcript_exon	Exon 6 of 6
	ZBTB8OS	NR_158773.1		n.541C>T		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB8OS	ENST00000468695.6	TSL:1 MANE Select	c.*26C>T		3_prime_UTR	Exon 7 of 7	ENSP00000417677.2
	ZBTB8OS	ENST00000436661.6	TSL:1	c.*66C>T		3_prime_UTR	Exon 6 of 6	ENSP00000413485.2
	ZBTB8OS	ENST00000341885.6	TSL:1	c.98-21486C>T		intron	N/A	ENSP00000343760.6

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

GnomAD2 exomes AF: 0.0759 AC: 16587 AN: 218412 AF XY: 0.0673

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 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

African (AFR) AF: 0.362 AC: 10526 AN: 29078

American (AMR) AF: 0.146 AC: 4702 AN: 32164

Ashkenazi Jewish (ASJ) AF: 0.0391 AC: 960 AN: 24522

East Asian (EAS) AF: 0.115 AC: 4417 AN: 38360

South Asian (SAS) AF: 0.0546 AC: 4162 AN: 76292

European-Finnish (FIN) AF: 0.0212 AC: 1114 AN: 52594

Middle Eastern (MID) AF: 0.0675 AC: 263 AN: 3894

European-Non Finnish (NFE) AF: 0.0350 AC: 35686 AN: 1019692

Other (OTH) AF: 0.0689 AC: 3842 AN: 55748

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

African (AFR) AF: 0.348 AC: 14410 AN: 41380

American (AMR) AF: 0.150 AC: 2291 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0383 AC: 133 AN: 3470

East Asian (EAS) AF: 0.115 AC: 598 AN: 5178

South Asian (SAS) AF: 0.0594 AC: 286 AN: 4814

European-Finnish (FIN) AF: 0.0217 AC: 229 AN: 10566

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0361 AC: 2452 AN: 67984

Other (OTH) AF: 0.132 AC: 279 AN: 2108

Alfa AF: 0.0837 Hom.: 371

Bravo AF: 0.159

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.61
PhyloP100		-0.12
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: rs3753603; hg19: chr1-33087437; COSMIC: COSV59384734; COSMIC: COSV59384734;