NM_001164310.3:c.502T>C

Variant names:

• chr9-35562691-A-G
• rs755804958
• NM_001164310.3:c.502T>C

Variant summary

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

The NM_001164310.3(CIMIP2B):​c.502T>C​(p.Tyr168His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y168N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CIMIP2B NM_001164310.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.33

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=0.34219137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMIP2B	NM_001164310.3	c.502T>C	p.Tyr168His	missense_variant	Exon 4 of 6	ENST00000399742.7	NP_001157782.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM166B	ENST00000399742.7	c.502T>C	p.Tyr168His	missense_variant	Exon 4 of 6	1	NM_001164310.3	ENSP00000382646.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000805 AC: 2 AN: 248406 Hom.: 0 AF XY: 0.00000742 AC XY: 1 AN XY: 134814

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461404 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 726940

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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

Bravo AF: 0.0000151

ExAC AF: 0.00000827 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.7	.;L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.6	.;D;.
REVEL	Benign	0.17
Sift	Uncertain	0.0050	.;D;.
Sift4G	Uncertain	0.0050	D;T;.
Polyphen		0.99, 1.0	.;D;D
Vest4		0.63
MutPred		0.27		Loss of phosphorylation at Y168 (P = 0.0171);Loss of phosphorylation at Y168 (P = 0.0171);Loss of phosphorylation at Y168 (P = 0.0171);
MVP		0.072
MPC		0.33
ClinPred		0.92	D
GERP RS		5.1
Varity_R		0.27
gMVP		0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs755804958; hg19: chr9-35562688;