12-108701237-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_014325.4(CORO1C):c.82C>T(p.Arg28Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000219 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 hom.)
• Consequence: CORO1C NM_014325.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.10

Genes affected

CORO1C (HGNC:2254): (coronin 1C) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.917

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CORO1C	NM_014325.4	c.82C>T	p.Arg28Trp	missense_variant	2/11	ENST00000261401.8
CORO1C	NM_001105237.2	c.241C>T	p.Arg81Trp	missense_variant	2/11
CORO1C	NM_001276471.2	c.82C>T	p.Arg28Trp	missense_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CORO1C	ENST00000261401.8	c.82C>T	p.Arg28Trp	missense_variant	2/11	1	NM_014325.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1461880 Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16 AN XY: 727242

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: 0.0000187

Gnomad4 NFE exome AF: 0.0000261

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000565 Hom.: 0

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

Oct 12, 2022

The c.82C>T (p.R28W) alteration is located in exon 2 (coding exon 1) of the CORO1C gene. This alteration results from a C to T substitution at nucleotide position 82, causing the arginine (R) at amino acid position 28 to be replaced by a tryptophan (W). 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	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
Cadd	Pathogenic	34
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.39	T;.;T;.;T;.;.;.;T
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Pathogenic	0.38	D
MetaRNN	Pathogenic	0.92	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.65	D
MutationAssessor	Pathogenic	3.2	M;.;M;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.94	D
PROVEAN	Pathogenic	-7.3	D;D;D;D;D;D;D;D;D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0020	D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;.;.;.;.;.
Polyphen		1.0	D;.;D;.;.;.;.;.;.
Vest4		0.80
MutPred		0.74		Gain of sheet (P = 0.0477);.;Gain of sheet (P = 0.0477);.;Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.77
MPC		1.7
ClinPred		1.0	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.84
gMVP		0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs969575661; hg19: chr12-109095013; COSMIC: COSV99775942; COSMIC: COSV99775942;