9-35562386-C-T

Variant names:

• chr9-35562386-C-T
• rs763217295
• NM_001164310.3:c.733G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001164310.3(CIMIP2B):​c.733G>A​(p.Val245Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,327,792 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: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: CIMIP2B NM_001164310.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37202644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMIP2B	NM_001164310.3	c.733G>A	p.Val245Met	missense_variant	Exon 5 of 6	ENST00000399742.7	NP_001157782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM166B	ENST00000399742.7	c.733G>A	p.Val245Met	missense_variant	Exon 5 of 6	1	NM_001164310.3	ENSP00000382646.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000218 AC: 29 AN: 1327792 Hom.: 0 Cov.: 33 AF XY: 0.0000139 AC XY: 9 AN XY: 646726

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000274

Gnomad4 SAS exome AF: 0.0000154

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000248

Gnomad4 OTH exome AF: 0.0000182

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.0000172 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.733G>A (p.V245M) alteration is located in exon 5 (coding exon 5) of the FAM166B gene. This alteration results from a G to A substitution at nucleotide position 733, causing the valine (V) at amino acid position 245 to be replaced by a methionine (M). 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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.67	T;T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Pathogenic	2.9	.;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.2	.;N
REVEL	Benign	0.29
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.012	D;D
Polyphen		1.0	.;D
Vest4		0.45
MutPred		0.29		.;Gain of disorder (P = 0.0741);
MVP		0.43
MPC		0.30
ClinPred		0.84	D
GERP RS		5.4
Varity_R		0.12
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs763217295; hg19: chr9-35562383;