rs757606947

Variant names:

• chr22-36999857-C-G
• NM_001163857.2:c.617G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-36999857-C-G
• chr22-36999857-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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 𝑓: 0.0000014 (0 hom.)
• Consequence: CIMIP4 NM_001163857.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.77

Genes affected

CIMIP4 (HGNC:28568): (ciliary microtubule inner protein 4)

ACMG classification

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
CIMIP4	NM_001163857.2	c.617G>C	p.Arg206Pro	missense_variant	Exon 4 of 6	ENST00000381821.2	NP_001157329.1
CIMIP4	NM_178552.4	c.362G>C	p.Arg121Pro	missense_variant	Exon 4 of 6		NP_848647.1
CIMIP4	XM_011530165.3	c.617G>C	p.Arg206Pro	missense_variant	Exon 5 of 7		XP_011528467.1
CIMIP4	XM_011530166.2	c.362G>C	p.Arg121Pro	missense_variant	Exon 4 of 6		XP_011528468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX33	ENST00000381821.2	c.617G>C	p.Arg206Pro	missense_variant	Exon 4 of 6	1	NM_001163857.2	ENSP00000371243.1
TEX33	ENST00000402860.7	c.362G>C	p.Arg121Pro	missense_variant	Exon 4 of 6	1		ENSP00000385179.3
TEX33	ENST00000405091.6	c.617G>C	p.Arg206Pro	missense_variant	Exon 5 of 7	5		ENSP00000386118.2
TEX33	ENST00000442538.5	c.191G>C	p.Arg64Pro	missense_variant	Exon 2 of 4	3		ENSP00000406640.1

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

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;