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. The variant received 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34219137).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164310.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIMIP2B	NM_001164310.3	MANE Select	c.502T>C	p.Tyr168His	missense	Exon 4 of 6	NP_001157782.1	A8MTA8-1
	CIMIP2B	NM_001287239.2		c.502T>C	p.Tyr168His	missense	Exon 4 of 6	NP_001274168.1
	CIMIP2B	NM_001099951.4		c.502T>C	p.Tyr168His	missense	Exon 4 of 6	NP_001093421.1	A8MTA8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIMIP2B	ENST00000399742.7	TSL:1 MANE Select	c.502T>C	p.Tyr168His	missense	Exon 4 of 6	ENSP00000382646.2	A8MTA8-1
	CIMIP2B	ENST00000447837.1	TSL:1	c.502T>C	p.Tyr168His	missense	Exon 4 of 6	ENSP00000412746.1	A8MTA8-2
	CIMIP2B	ENST00000492890.5	TSL:5	c.469T>C	p.Tyr157His	missense	Exon 4 of 6	ENSP00000513459.1	A0A8V8TLC2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000805 AC: 2 AN: 248406 AF XY: 0.00000742

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111794

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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 v4.9

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
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.3
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.17
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.63
MutPred		0.27		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
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs755804958; hg19: chr9-35562688;