NM_001354640.2:c.988+1G>C

Variant names:

• chr14-23102628-C-G
• NM_001354640.2:c.988+1G>C

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001354640.2(CIROP):​c.988+1G>C variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CIROP NM_001354640.2 splice_donor, intron
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.63

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

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-23102628-C-G is Pathogenic according to our data. Variant chr14-23102628-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 3390959.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIROP	NM_001354640.2	c.988+1G>C		splice_donor_variant, intron_variant	Intron 8 of 15	ENST00000637218.2	NP_001341569.1
CIROP	NM_001402427.1	c.823+1G>C		splice_donor_variant, intron_variant	Intron 6 of 13		NP_001389356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIROP	ENST00000637218.2	c.988+1G>C		splice_donor_variant, intron_variant	Intron 8 of 15	5	NM_001354640.2	ENSP00000489869.1
CIROP	ENST00000644000.1	c.814+1G>C		splice_donor_variant, intron_variant	Intron 6 of 13			ENSP00000493582.1
CIROP	ENST00000642668.1	c.739+1G>C		splice_donor_variant, intron_variant	Intron 6 of 12			ENSP00000495729.1
CIROP	ENST00000644147.1	n.745+1G>C		splice_donor_variant, intron_variant	Intron 5 of 8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Trichothiodystrophy 1, photosensitive Pathogenic:1

Dec 17, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Benign	0.69
FATHMM_MKL	Uncertain	0.91	D
GERP RS		4.6

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: chr14-23571837;