chr9-137245158-C-G

Variant names:

• chr9-137245158-C-G
• NM_001001710.3:c.583G>C

Variant summary

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

The NM_001001710.3(CIMIP2A):​c.583G>C​(p.Asp195His) 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. 12/20 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: 0.397

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2586701).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMIP2A	NM_001001710.3	c.583G>C	p.Asp195His	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.583G>C	p.Asp195His	missense_variant	Exon 4 of 7	1	NM_001001710.3	ENSP00000344729.4
FAM166A	ENST00000484720.1	c.664G>C	p.Asp222His	missense_variant	Exon 3 of 3	3		ENSP00000420741.1
FAM166A	ENST00000471784.2	n.638G>C		non_coding_transcript_exon_variant	Exon 4 of 6	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.583G>C (p.D195H) alteration is located in exon 4 (coding exon 4) of the FAM166A gene. This alteration results from a G to C substitution at nucleotide position 583, causing the aspartic acid (D) at amino acid position 195 to be replaced by a histidine (H). 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	0.18
BayesDel_addAF	Benign	0.0014	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;T
Eigen	Benign	0.18
Eigen_PC	Benign	0.028
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.5	N;N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.046	D;.
Polyphen		1.0	D;.
Vest4		0.54
MutPred		0.54		Gain of sheet (P = 0.1208);.;
MVP		0.18
MPC		0.0078
ClinPred		0.83	D
GERP RS		4.3
Varity_R		0.11
gMVP		0.60

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: chr9-140139610;