NM_025057.3:c.634C>T

Variant names:

• chr14-74046117-C-T
• rs371096556
• NM_025057.3:c.634C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025057.3(BBOF1):​c.634C>T​(p.His212Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,607,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: BBOF1 NM_025057.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42
• Publications: 1 publications found

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

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=0.1959981).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025057.3. 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
	BBOF1	NM_025057.3	MANE Select	c.634C>T	p.His212Tyr	missense	Exon 6 of 12	NP_079333.2	Q8ND07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BBOF1	ENST00000394009.5	TSL:2 MANE Select	c.634C>T	p.His212Tyr	missense	Exon 6 of 12	ENSP00000377577.3	Q8ND07
	BBOF1	ENST00000901146.1		c.490C>T	p.His164Tyr	missense	Exon 5 of 11	ENSP00000571205.1
	BBOF1	ENST00000901145.1		c.634C>T	p.His212Tyr	missense	Exon 6 of 10	ENSP00000571204.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152164 Hom.: 0 Cov.: 32

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000378 AC: 9 AN: 238122 AF XY: 0.0000465

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000837

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000289 AC: 42 AN: 1455228 Hom.: 0 Cov.: 30 AF XY: 0.0000277 AC XY: 20 AN XY: 723180

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 43668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25920

East Asian (EAS) AF: 0.00 AC: 0 AN: 39594

South Asian (SAS) AF: 0.00 AC: 0 AN: 84710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000370 AC: 41 AN: 1108884

Other (OTH) AF: 0.0000166 AC: 1 AN: 60164

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74462

African (AFR) AF: 0.00 AC: 0 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000965 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000581 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0032	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.067
Sift	Benign	0.69	T
Sift4G	Uncertain	0.047	D
Polyphen		0.78	P
Vest4		0.49
MVP		0.51
MPC		0.32
ClinPred		0.25	T
GERP RS		5.9
Varity_R		0.17
gMVP		0.20
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs371096556; hg19: chr14-74512820;