chr9-35563068-C-T

Variant names:

• chr9-35563068-C-T
• rs771226899
• NM_001164310.3:c.299G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001164310.3(CIMIP2B):​c.299G>A​(p.Arg100Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 1,613,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R100W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000072 (0 hom.)
• Consequence: CIMIP2B NM_001164310.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0160
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10423264).
• BP6: Variant 9-35563068-C-T is Benign according to our data. Variant chr9-35563068-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3833535.Status of the report is criteria_provided_single_submitter, 1 stars.

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.299G>A	p.Arg100Gln	missense	Exon 3 of 6	NP_001157782.1	A8MTA8-1
	CIMIP2B	NM_001287239.2		c.299G>A	p.Arg100Gln	missense	Exon 3 of 6	NP_001274168.1
	CIMIP2B	NM_001287238.2		c.299G>A	p.Arg100Gln	missense	Exon 3 of 6	NP_001274167.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIMIP2B	ENST00000399742.7	TSL:1 MANE Select	c.299G>A	p.Arg100Gln	missense	Exon 3 of 6	ENSP00000382646.2	A8MTA8-1
	CIMIP2B	ENST00000447837.1	TSL:1	c.299G>A	p.Arg100Gln	missense	Exon 3 of 6	ENSP00000412746.1	A8MTA8-2
	CIMIP2B	ENST00000492890.5	TSL:5	c.266G>A	p.Arg89Gln	missense	Exon 3 of 6	ENSP00000513459.1	A0A8V8TLC2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000281 AC: 7 AN: 248928 AF XY: 0.0000444

Gnomad AFR exome AF: 0.0000647

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: 0.0000355

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000718 AC: 105 AN: 1461624 Hom.: 0 Cov.: 34 AF XY: 0.0000729 AC XY: 53 AN XY: 727078

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.0000818 AC: 91 AN: 1111826

Other (OTH) AF: 0.0000497 AC: 3 AN: 60364

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152188 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74340

African (AFR) AF: 0.0000241 AC: 1 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000248 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.080	N
PhyloP100		0.016
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.070
Sift	Benign	0.28	T
Sift4G	Benign	0.43	T
Polyphen		0.016	B
Vest4		0.11
MVP		0.040
MPC		0.048
ClinPred		0.051	T
GERP RS		-1.5
Varity_R		0.073
gMVP		0.22
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs771226899; hg19: chr9-35563065;