rs757606947

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001163857.2(CIMIP4):​c.617G>C​(p.Arg206Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R206Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CIMIP4
NM_001163857.2 missense

Scores

6
7
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.77
Variant links:
Genes affected
CIMIP4 (HGNC:28568): (ciliary microtubule inner protein 4)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CIMIP4NM_001163857.2 linkc.617G>C p.Arg206Pro missense_variant Exon 4 of 6 ENST00000381821.2 NP_001157329.1 O43247-1
CIMIP4NM_178552.4 linkc.362G>C p.Arg121Pro missense_variant Exon 4 of 6 NP_848647.1 O43247-2
CIMIP4XM_011530165.3 linkc.617G>C p.Arg206Pro missense_variant Exon 5 of 7 XP_011528467.1 O43247-1
CIMIP4XM_011530166.2 linkc.362G>C p.Arg121Pro missense_variant Exon 4 of 6 XP_011528468.1 O43247-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TEX33ENST00000381821.2 linkc.617G>C p.Arg206Pro missense_variant Exon 4 of 6 1 NM_001163857.2 ENSP00000371243.1 O43247-1
TEX33ENST00000402860.7 linkc.362G>C p.Arg121Pro missense_variant Exon 4 of 6 1 ENSP00000385179.3 O43247-2
TEX33ENST00000405091.6 linkc.617G>C p.Arg206Pro missense_variant Exon 5 of 7 5 ENSP00000386118.2 O43247-1
TEX33ENST00000442538.5 linkc.191G>C p.Arg64Pro missense_variant Exon 2 of 4 3 ENSP00000406640.1 H0Y6N4

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461434
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727042
show subpopulations
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.95
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.29
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.14
.;T;T
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.81
T;.;T
M_CAP
Benign
0.025
D
MetaRNN
Pathogenic
0.75
D;D;D
MetaSVM
Benign
-0.46
T
MutationAssessor
Uncertain
2.6
.;M;M
PrimateAI
Uncertain
0.58
T
PROVEAN
Pathogenic
-5.7
D;D;D
REVEL
Uncertain
0.32
Sift
Uncertain
0.011
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
.;D;D
Vest4
0.88
MutPred
0.55
.;Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);
MVP
0.15
MPC
0.16
ClinPred
0.99
D
GERP RS
4.9
Varity_R
0.88
gMVP
0.47

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: chr22-37395898; API