9-137245095-T-C

Variant names:

• chr9-137245095-T-C
• NM_001001710.3:c.646A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001001710.3(CIMIP2A):​c.646A>G​(p.Ile216Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CIMIP2A NM_001001710.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.956

Genes affected

CIMIP2A (HGNC:33818): (ciliary microtubule inner protein 2A) Located in ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMIP2A	NM_001001710.3	c.646A>G	p.Ile216Val	missense_variant	Exon 4 of 7	ENST00000344774.6	NP_001001710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM166A	ENST00000344774.6	c.646A>G	p.Ile216Val	missense_variant	Exon 4 of 7	1	NM_001001710.3	ENSP00000344729.4
FAM166A	ENST00000471784.2	n.701A>G		non_coding_transcript_exon_variant	Exon 4 of 6	2
FAM166A	ENST00000484720.1	c.*57A>G		downstream_gene_variant		3		ENSP00000420741.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.646A>G (p.I216V) alteration is located in exon 4 (coding exon 4) of the FAM166A gene. This alteration results from a A to G substitution at nucleotide position 646, causing the isoleucine (I) at amino acid position 216 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	Benign	0.13
BayesDel_addAF	Benign	-0.0096	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0088	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.28
Sift	Benign	0.17	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.53
MutPred		0.78		Loss of helix (P = 0.1299);
MVP		0.12
MPC		0.011
ClinPred		0.88	D
GERP RS		5.2
Varity_R		0.043
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-140139547;