1-16924471-A-G

Position:

• chr1-16924471-A-G

Variant summary

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

The NM_014675.5(CROCC):​c.343A>G​(p.Ser115Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 52)
• Consequence: CROCC NM_014675.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.25

Genes affected

CROCC (HGNC:21299): (ciliary rootlet coiled-coil, rootletin) Predicted to enable kinesin binding activity and structural molecule activity. Involved in several processes, including centriole-centriole cohesion; positive regulation of cilium assembly; and positive regulation of protein localization to cilium. Located in cytoskeleton; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CROCC (HGNC:):

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/exons	MANE	Protein	UniProt
CROCC	NM_014675.5	c.343A>G	p.Ser115Gly	missense_variant	3/37	ENST00000375541.10	NP_055490.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CROCC	ENST00000375541.10	c.343A>G	p.Ser115Gly	missense_variant	3/37	5	NM_014675.5	ENSP00000364691.4
CROCC	ENST00000445545.6	c.190A>G	p.Ser64Gly	missense_variant	2/24	5		ENSP00000402626.2
CROCC	ENST00000467938.5	c.30+1673A>G		intron_variant		2		ENSP00000480016.1
CROCC	ENST00000466256.6	n.126-5815A>G		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 52

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 52

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.343A>G (p.S115G) alteration is located in exon 3 (coding exon 3) of the CROCC gene. This alteration results from a A to G substitution at nucleotide position 343, causing the serine (S) at amino acid position 115 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Pathogenic	26
DANN	Benign	0.95
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-0.99	T
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.14
Sift	Benign	0.037	D
Sift4G	Uncertain	0.030	D
Vest4		0.65
MutPred		0.15		Loss of phosphorylation at S115 (P = 0.033);
MVP		0.32
MPC		0.25
ClinPred		0.87	D
GERP RS		5.1
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -14

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: chr1-17250966;