9-137243755-T-C

Variant names:

• chr9-137243755-T-C
• NM_001001710.3:c.899A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001710.3(CIMIP2A):​c.899A>G​(p.Asn300Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 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: 1.17

Genes affected

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

TUBB4B (HGNC:20771): (tubulin beta 4B class IVb) Enables double-stranded RNA binding activity. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in microtubule. Implicated in Leber congenital amaurosis with early-onset deafness. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1648632).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMIP2A	NM_001001710.3	c.899A>G	p.Asn300Ser	missense_variant	Exon 7 of 7	ENST00000344774.6	NP_001001710.1
TUBB4B	NM_006088.6	c.*199T>C		downstream_gene_variant		ENST00000340384.5	NP_006079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM166A	ENST00000344774.6	c.899A>G	p.Asn300Ser	missense_variant	Exon 7 of 7	1	NM_001001710.3	ENSP00000344729.4
FAM166A	ENST00000471784.2	n.1549A>G		non_coding_transcript_exon_variant	Exon 6 of 6	2
TUBB4B	ENST00000340384.5	c.*199T>C		downstream_gene_variant		1	NM_006088.6	ENSP00000341289.4
TUBB4B	ENST00000604929.1	n.*49T>C		downstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.899A>G (p.N300S) alteration is located in exon 7 (coding exon 7) of the FAM166A gene. This alteration results from a A to G substitution at nucleotide position 899, causing the asparagine (N) at amino acid position 300 to be replaced by a serine (S). 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	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.54
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.096
Sift	Benign	0.23	T
Sift4G	Benign	0.16	T
Polyphen		0.23	B
Vest4		0.39
MutPred		0.35		Gain of glycosylation at N300 (P = 0.0423);
MVP		0.11
MPC		0.0032
ClinPred		0.14	T
GERP RS		3.9
Varity_R		0.054
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr9-140138207;