14-23102235-C-A

Position:

• chr14-23102235-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

CIROP (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 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 id is 1344493.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIROP	NM_001354640.2	c.1166G>T	p.Arg389Ile	missense_variant	10/16	ENST00000637218.2	NP_001341569.1
CIROP	NM_001402427.1	c.1001G>T	p.Arg334Ile	missense_variant	8/14		NP_001389356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIROP	ENST00000637218.2	c.1166G>T	p.Arg389Ile	missense_variant	10/16	5	NM_001354640.2	ENSP00000489869.1
CIROP	ENST00000644000.1	c.992G>T	p.Arg331Ile	missense_variant	8/14			ENSP00000493582.1
CIROP	ENST00000642668.1	c.917G>T	p.Arg306Ile	missense_variant	8/13			ENSP00000495729.1
CIROP	ENST00000644147.1	n.923G>T		non_coding_transcript_exon_variant	7/9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Heterotaxy, visceral, 12, autosomal Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

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;T;T
MetaRNN	Uncertain	0.53	D;D;D
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-23571444;