chr9-35563080-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164310.3. 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
	CIMIP2B	NM_001164310.3	MANE Select	c.287G>T	p.Gly96Val	missense splice_region	Exon 3 of 6	NP_001157782.1	A8MTA8-1
	CIMIP2B	NM_001287239.2		c.287G>T	p.Gly96Val	missense splice_region	Exon 3 of 6	NP_001274168.1
	CIMIP2B	NM_001287238.2		c.287G>T	p.Gly96Val	missense splice_region	Exon 3 of 6	NP_001274167.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIMIP2B	ENST00000399742.7	TSL:1 MANE Select	c.287G>T	p.Gly96Val	missense splice_region	Exon 3 of 6	ENSP00000382646.2	A8MTA8-1
	CIMIP2B	ENST00000447837.1	TSL:1	c.287G>T	p.Gly96Val	missense splice_region	Exon 3 of 6	ENSP00000412746.1	A8MTA8-2
	CIMIP2B	ENST00000492890.5	TSL:5	c.254G>T	p.Gly85Val	missense splice_region	Exon 3 of 6	ENSP00000513459.1	A0A8V8TLC2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000378

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	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
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.84	D
MetaSVM	Uncertain	-0.043	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.8
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-8.2	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.88
MutPred		0.61		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
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs1822276905; hg19: chr9-35563077;