9-35563080-C-A

Variant names:

• chr9-35563080-C-A
• rs1822276905
• NM_001164310.3:c.287G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001164310.3(CIMIP2B):​c.287G>T​(p.Gly96Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIMIP2B NM_001164310.3 missense, splice_region
• Scores: Splicing: ADA: 0.9999
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84

Genes affected

CIMIP2B (HGNC:34242): (ciliary microtubule inner protein 2B)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.839

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMIP2B	NM_001164310.3	c.287G>T	p.Gly96Val	missense_variant, splice_region_variant	Exon 3 of 6	ENST00000399742.7	NP_001157782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM166B	ENST00000399742.7	c.287G>T	p.Gly96Val	missense_variant, splice_region_variant	Exon 3 of 6	1	NM_001164310.3	ENSP00000382646.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.287G>T (p.G96V) alteration is located in exon 3 (coding exon 3) of the FAM166B gene. This alteration results from a G to T substitution at nucleotide position 287, causing the glycine (G) at amino acid position 96 to be replaced by a valine (V). 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	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	33
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	.;T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Uncertain	-0.043	T
MutationAssessor	Benign	1.7	.;L;L
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-8.2	.;D;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.0030	.;D;.
Sift4G	Pathogenic	0.0	D;D;.
Polyphen		1.0	.;D;D
Vest4		0.88
MutPred		0.61		Loss of catalytic residue at P92 (P = 0.0836);Loss of catalytic residue at P92 (P = 0.0836);Loss of catalytic residue at P92 (P = 0.0836);
MVP		0.34
MPC		0.33
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.80
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.98
SpliceAI score (max)		0.17		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: rs1822276905; hg19: chr9-35563077;