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. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB8OS	NM_178547.5	c.457G>T	p.Val153Phe	missense_variant	Exon 7 of 7	ENST00000468695.6	NP_848642.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB8OS	ENST00000468695.6	c.457G>T	p.Val153Phe	missense_variant	Exon 7 of 7	1	NM_178547.5	ENSP00000417677.2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000209

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T;.;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.96	D;.;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-0.68	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.3	D;N;.
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D;T;.
Sift4G	Pathogenic	0.0010	D;D;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

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: rs773929207; hg19: chr1-33087510;