1-32621909-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/19 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
• 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 0 ACMG points.

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

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>C	p.Val153Leu	missense	Exon 7 of 7	NP_848642.2	Q8IWT0-1
	ZBTB8OS	NM_001366264.1		c.529G>C	p.Val177Leu	missense	Exon 7 of 7	NP_001353193.1
	ZBTB8OS	NM_001308135.2		c.472G>C	p.Val158Leu	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>C	p.Val153Leu	missense	Exon 7 of 7	ENSP00000417677.2	Q8IWT0-1
	ZBTB8OS	ENST00000436661.6	TSL:1	c.404G>C	p.Gly135Ala	missense	Exon 6 of 6	ENSP00000413485.2	Q8IWT0-2
	ZBTB8OS	ENST00000341885.6	TSL:1	c.98-21559G>C		intron	N/A	ENSP00000343760.6	F6SII6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.00070
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.7
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0080	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
Mutation Taster		=80/20	polymorphism

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;