14-74019496-G-C

Variant summary

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

The NM_025057.3(BBOF1):c.18G>C(p.Lys6Asn) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBOF1 NM_025057.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.486

Genes affected

BBOF1 (HGNC:19855): (basal body orientation factor 1) Predicted to be involved in motile cilium assembly. Predicted to be located in ciliary basal body. [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=0.20439008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BBOF1	NM_025057.3	c.18G>C	p.Lys6Asn	missense_variant	1/12	ENST00000394009.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BBOF1	ENST00000394009.5	c.18G>C	p.Lys6Asn	missense_variant	1/12	2	NM_025057.3	P1
BBOF1	ENST00000463558.3	c.-174G>C		5_prime_UTR_variant	1/4	2
BBOF1	ENST00000464394.5	c.-174G>C		5_prime_UTR_variant	1/6	3
BBOF1	ENST00000489323.5	n.51G>C		non_coding_transcript_exon_variant	1/6	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 19, 2023

The c.18G>C (p.K6N) alteration is located in exon 1 (coding exon 1) of the BBOF1 gene. This alteration results from a G to C substitution at nucleotide position 18, causing the lysine (K) at amino acid position 6 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	21
Dann	Benign	0.95
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.15
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.19
MutPred		0.14		Loss of methylation at K6 (P = 0.0118);
MVP		0.17
MPC		0.085
ClinPred		0.41	T
GERP RS		-0.98
Varity_R		0.15
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs879931110; hg19: chr14-74486199;