Variant 1-16924466-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014675.5(CROCC):c.338C>G(p.Ala113Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,898 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A113V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 52)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CROCC
NM_014675.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

Variant links:

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 links:

CROCC (HGNC:):

CROCC links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.338C>G	p.Ala113Gly	missense_variant	3/37	ENST00000375541.10	NP_055490.4	Q5TZA2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CROCC	ENST00000375541.10 linkuse as main transcript	c.338C>G	p.Ala113Gly	missense_variant	3/37	5	NM_014675.5	ENSP00000364691.4	Q5TZA2-1
CROCC	ENST00000445545.6 linkuse as main transcript	c.185C>G	p.Ala62Gly	missense_variant	2/24	5		ENSP00000402626.2	B1AKD8
CROCC	ENST00000467938.5 linkuse as main transcript	c.30+1668C>G		intron_variant		2		ENSP00000480016.1	A0A087WW81
CROCC	ENST00000466256.6 linkuse as main transcript	n.126-5820C>G		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459898

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725972

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.338C>G (p.A113G) alteration is located in exon 3 (coding exon 3) of the CROCC gene. This alteration results from a C to G substitution at nucleotide position 338, causing the alanine (A) at amino acid position 113 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.5

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.054

Vest4

0.60

MutPred

0.22

Gain of relative solvent accessibility (P = 0.0479);

MVP

0.35

MPC

0.19

ClinPred

0.78

GERP RS

5.1

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.39

Position offset: -9

DS_DL_spliceai

0.30

Position offset: 13

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over