12-108648647-G-T

Position:

• chr12-108648647-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014325.4(CORO1C):​c.1263C>A​(p.Asp421Glu) 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. 13/21 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: 0.398

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060416073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CORO1C	NM_014325.4	c.1263C>A	p.Asp421Glu	missense_variant	10/11	ENST00000261401.8	NP_055140.1
CORO1C	NM_001105237.2	c.1422C>A	p.Asp474Glu	missense_variant	10/11		NP_001098707.1
CORO1C	NM_001276471.2	c.1263C>A	p.Asp421Glu	missense_variant	10/11		NP_001263400.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CORO1C	ENST00000261401.8	c.1263C>A	p.Asp421Glu	missense_variant	10/11	1	NM_014325.4	ENSP00000261401.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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 16, 2023

The c.1263C>A (p.D421E) alteration is located in exon 10 (coding exon 9) of the CORO1C gene. This alteration results from a C to A substitution at nucleotide position 1263, causing the aspartic acid (D) at amino acid position 421 to be replaced by a glutamic acid (E). 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	0.086
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T;.;T;T;T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.70	.;T;T;T;T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.060	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.6	N;.;N;.;.;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.19	N;N;N;N;N;N
REVEL	Benign	0.077
Sift	Benign	0.20	T;T;T;T;T;T
Sift4G	Benign	0.52	T;T;T;T;T;T
Polyphen		0.0	B;.;B;.;.;.
Vest4		0.11
MutPred		0.15		Gain of methylation at K418 (P = 0.0955);.;Gain of methylation at K418 (P = 0.0955);.;.;.;
MVP		0.24
MPC		0.61
ClinPred		0.23	T
GERP RS		3.8
Varity_R		0.064
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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: chr12-109042423;