rs773929207

Variant names:

• chr1-32621909-C-A
• rs773929207
• NM_178547.5:c.457G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-32621909-C-A
• chr1-32621909-C-G
• chr1-32621909-C-T

Variant summary

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

The NM_178547.5(ZBTB8OS):​c.457G>T​(p.Val153Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,592,488 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V153I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZBTB8OS NM_178547.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB8OS	NM_178547.5	MANE Select	c.457G>T	p.Val153Phe	missense	Exon 7 of 7	NP_848642.2	Q8IWT0-1
	ZBTB8OS	NM_001366264.1		c.529G>T	p.Val177Phe	missense	Exon 7 of 7	NP_001353193.1
	ZBTB8OS	NM_001308135.2		c.472G>T	p.Val158Phe	missense	Exon 6 of 6	NP_001295064.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB8OS	ENST00000468695.6	TSL:1 MANE Select	c.457G>T	p.Val153Phe	missense	Exon 7 of 7	ENSP00000417677.2	Q8IWT0-1
	ZBTB8OS	ENST00000436661.6	TSL:1	c.404G>T	p.Gly135Val	missense	Exon 6 of 6	ENSP00000413485.2	Q8IWT0-2
	ZBTB8OS	ENST00000341885.6	TSL:1	c.98-21559G>T		intron	N/A	ENSP00000343760.6	F6SII6

Frequencies

GnomAD3 genomes AF: 0.00000666 AC: 1 AN: 150222 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1442266 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 716918

African (AFR) AF: 0.00 AC: 0 AN: 32250

American (AMR) AF: 0.00 AC: 0 AN: 39416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25820

East Asian (EAS) AF: 0.00 AC: 0 AN: 39346

South Asian (SAS) AF: 0.00 AC: 0 AN: 80606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4508

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108308

Other (OTH) AF: 0.00 AC: 0 AN: 59580

GnomAD4 genome AF: 0.00000666 AC: 1 AN: 150222 Hom.: 0 Cov.: 31 AF XY: 0.0000137 AC XY: 1 AN XY: 73128

African (AFR) AF: 0.00 AC: 0 AN: 40698

American (AMR) AF: 0.00 AC: 0 AN: 15070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67830

Other (OTH) AF: 0.00 AC: 0 AN: 2064

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.68	T
PhyloP100		1.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.97	D
Vest4		0.57
MutPred		0.76		Loss of sheet (P = 0.0817)
MVP		0.55
MPC		0.82
ClinPred		0.99	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.50
Mutation Taster		=48/52	disease causing

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: rs773929207; hg19: chr1-33087510;