12-108647457-A-C

Position:

• chr12-108647457-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014325.4(CORO1C):​c.1371T>G​(p.Asn457Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CORO1C NM_014325.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.52

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]

CORO1C (HGNC:):

ACMG classification

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=0.118624896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORO1C	NM_014325.4	c.1371T>G	p.Asn457Lys	missense_variant	11/11	ENST00000261401.8	NP_055140.1
CORO1C	NM_001105237.2	c.1530T>G	p.Asn510Lys	missense_variant	11/11		NP_001098707.1
CORO1C	NM_001276471.2	c.1371T>G	p.Asn457Lys	missense_variant	11/11		NP_001263400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORO1C	ENST00000261401.8	c.1371T>G	p.Asn457Lys	missense_variant	11/11	1	NM_014325.4	ENSP00000261401.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Nov 09, 2023

The c.1371T>G (p.N457K) alteration is located in exon 11 (coding exon 10) of the CORO1C gene. This alteration results from a T to G substitution at nucleotide position 1371, causing the asparagine (N) at amino acid position 457 to be replaced by a lysine (K). 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	0.091
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.85
DEOGEN2	Benign	0.017	T;.;T;T;T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.089
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.84	.;T;T;T;T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N;.;N;.;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.83	N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T;T;T;T;T
Sift4G	Benign	0.96	T;T;T;T;T;T
Polyphen		0.0	B;.;B;.;.;.
Vest4		0.28
MutPred		0.34		Gain of methylation at N457 (P = 0.0158);.;Gain of methylation at N457 (P = 0.0158);.;.;.;
MVP		0.42
MPC		0.76
ClinPred		0.66	D
GERP RS		5.9
Varity_R		0.052
gMVP		0.036

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: rs1361046719; hg19: chr12-109041233;