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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014675.5(CROCC):c.338C>T(p.Ala113Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,612,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 52)

Exomes 𝑓: 0.000012 ( 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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25599515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CROCC	NM_014675.5 linkuse as main transcript	c.338C>T	p.Ala113Val	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>T	p.Ala113Val	missense_variant	3/37	5	NM_014675.5	ENSP00000364691.4	Q5TZA2-1
CROCC	ENST00000445545.6 linkuse as main transcript	c.185C>T	p.Ala62Val	missense_variant	2/24	5		ENSP00000402626.2	B1AKD8
CROCC	ENST00000467938.5 linkuse as main transcript	c.30+1668C>T		intron_variant		2		ENSP00000480016.1	A0A087WW81
CROCC	ENST00000466256.6 linkuse as main transcript	n.126-5820C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152280

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248798

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1459888

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

725968

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000378

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

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

Mar 29, 2022

The c.338C>T (p.A113V) alteration is located in exon 3 (coding exon 3) of the CROCC gene. This alteration results from a C to T substitution at nucleotide position 338, causing the alanine (A) at amino acid position 113 to be replaced by a valine (V). 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

0.24

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.073

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.8

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.023

Vest4

0.43

MutPred

0.14

Gain of helix (P = 0.0861);

MVP

0.33

MPC

0.27

ClinPred

0.76

GERP RS

5.1

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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