Genetic Variant CORO6:p.Arg456Leu (chr17-29615784-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_032854.4(CORO6):c.1367G>T(p.Arg456Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000199 in 1,558,518 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

CORO6
NM_032854.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

Variant links:

Genes affected

CORO6 (HGNC:21356): (coronin 6) Predicted to enable actin filament binding activity. Predicted to be involved in actin filament organization and cell migration. [provided by Alliance of Genome Resources, Apr 2022]

CORO6 links:

ABHD15-AS1 (HGNC:49685): (ABHD15 antisense RNA 1)

ABHD15-AS1 links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
CORO6	NM_032854.4 link	c.1367G>T	p.Arg456Leu	missense_variant	Exon 11 of 11	ENST00000388767.8	NP_116243.2	Q6QEF8-5B3KRY9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORO6	ENST00000388767.8 link	c.1367G>T	p.Arg456Leu	missense_variant	Exon 11 of 11	2	NM_032854.4	ENSP00000373419.3		Q6QEF8-5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000288

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:

0.000478

GnomAD3 exomes

AF:

0.0000438

AC:

AN:

159920

Hom.:

AF XY:

0.0000117

AC XY:

AN XY:

85822

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000783

Gnomad ASJ exome

AF:

0.000592

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1406380

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

694640

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000547

Gnomad4 ASJ exome

AF:

0.000555

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000369

Gnomad4 OTH exome

AF:

0.000137

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000591

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.0000172

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1367G>T (p.R456L) alteration is located in exon 10 (coding exon 10) of the CORO6 gene. This alteration results from a G to T substitution at nucleotide position 1367, causing the arginine (R) at amino acid position 456 to be replaced by a leucine (L). 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

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.12

.;.;T;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

D;.;D;D

M_CAP

Pathogenic

0.32

MetaRNN

Uncertain

0.69

D;D;D;D

MetaSVM

Uncertain

0.11

MutationAssessor

Uncertain

2.9

M;M;.;.

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.6

D;.;.;.

REVEL

Uncertain

0.56

Sift

Uncertain

0.024

D;.;.;.

Sift4G

Uncertain

0.024

D;D;D;D

Polyphen

1.0

D;D;.;.

Vest4

0.60

MVP

0.92

MPC

1.1

ClinPred

0.85

GERP RS

4.2

gMVP

0.32

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

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