1-32621909-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178547.5(ZBTB8OS):​c.457G>C​(p.Val153Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. 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: not found (cov: 31)
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2272487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB8OS	NM_178547.5	c.457G>C	p.Val153Leu	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>C	p.Val153Leu	missense_variant	Exon 7 of 7	1	NM_178547.5	ENSP00000417677.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.058	T;.;T
Eigen	Benign	-0.00070
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.95	D;.;D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.5	N;N;.
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D;T;.
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.44	B;.;.
Vest4		0.32
MutPred		0.78		Loss of sheet (P = 0.0817);.;.;
MVP		0.29
MPC		0.31
ClinPred		0.76	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.27

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;