chr14-23103740-C-A

Variant names:

• chr14-23103740-C-A
• NM_001354640.2:c.538G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001354640.2(CIROP):​c.538G>T​(p.Gly180Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 550,714 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: CIROP NM_001354640.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIROP	NM_001354640.2	c.538G>T	p.Gly180Trp	missense_variant	Exon 4 of 16	ENST00000637218.2	NP_001341569.1
CIROP	NM_001402427.1	c.547G>T	p.Gly183Trp	missense_variant	Exon 4 of 14		NP_001389356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIROP	ENST00000637218.2	c.538G>T	p.Gly180Trp	missense_variant	Exon 4 of 16	5	NM_001354640.2	ENSP00000489869.1
CIROP	ENST00000644000.1	c.538G>T	p.Gly180Trp	missense_variant	Exon 4 of 14			ENSP00000493582.1
CIROP	ENST00000642668.1	c.463G>T	p.Gly155Trp	missense_variant	Exon 4 of 13			ENSP00000495729.1
CIROP	ENST00000644147.1	n.595G>T		non_coding_transcript_exon_variant	Exon 4 of 9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000182 AC: 1 AN: 550714 Hom.: 0 Cov.: 0 AF XY: 0.00000335 AC XY: 1 AN XY: 298134

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: 0.0000159

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Benign	0.82
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.58	T;T;T
MetaRNN	Uncertain	0.51	D;D;D
GERP RS		4.8
Varity_R		0.34
gMVP		0.77

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: chr14-23572949;