14-23102235-C-A

Variant names:

• chr14-23102235-C-A
• rs2140282332
• NM_001354640.2:c.1166G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_001354640.2(CIROP):​c.1166G>T​(p.Arg389Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIROP NM_001354640.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.90
• Publications: 0 publications found

Genes affected

CIROP (HGNC:53647): (ciliated left-right organizer metallopeptidase) Predicted to enable peptidase activity. Predicted to be involved in cell adhesion and proteolysis. Predicted to be integral component of membrane. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-23102235-C-A is Pathogenic according to our data. Variant chr14-23102235-C-A is described in ClinVar as Pathogenic. ClinVar VariationId is 1344493.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354640.2. 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
	CIROP	NM_001354640.2	MANE Select	c.1166G>T	p.Arg389Ile	missense	Exon 10 of 16	NP_001341569.1	A0A1B0GTW7-1
	CIROP	NM_001402427.1		c.1001G>T	p.Arg334Ile	missense	Exon 8 of 14	NP_001389356.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIROP	ENST00000637218.2	TSL:5 MANE Select	c.1166G>T	p.Arg389Ile	missense	Exon 10 of 16	ENSP00000489869.1	A0A1B0GTW7-1
	CIROP	ENST00000644000.1		c.992G>T	p.Arg331Ile	missense	Exon 8 of 14	ENSP00000493582.1	A0A1B0GTW7-2
	CIROP	ENST00000642668.1		c.917G>T	p.Arg306Ile	missense	Exon 8 of 13	ENSP00000495729.1	A0A2R8Y752

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Heterotaxy, visceral, 12, autosomal (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Benign	0.84
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T
MetaRNN	Uncertain	0.53	D
PhyloP100		5.9
GERP RS		5.0
Varity_R		0.43
gMVP		0.89

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2140282332; hg19: chr14-23571444;