9-35563080-C-T

Variant names:

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

Variant summary

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

The NM_001164310.3(CIMIP2B):​c.287G>A​(p.Gly96Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,592 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CIMIP2B NM_001164310.3 missense, splice_region
• Scores: Splicing: ADA: 0.9998
• Clinical Significance: Not reported in ClinVar
• 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, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMIP2B	NM_001164310.3	c.287G>A	p.Gly96Asp	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>A	p.Gly96Asp	missense_variant, splice_region_variant	Exon 3 of 6	1	NM_001164310.3	ENSP00000382646.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461592 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727050

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	.;T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0094	T
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Uncertain	-0.043	T
MutationAssessor	Benign	1.7	.;L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.4	.;D;.
REVEL	Uncertain	0.47
Sift	Uncertain	0.0040	.;D;.
Sift4G	Pathogenic	0.0	D;D;.
Polyphen		1.0	.;D;D
Vest4		0.92
MutPred		0.59		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		0.24
MPC		0.33
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.64
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.93
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-35563077;