17-29615764-T-C

Variant names:

• chr17-29615764-T-C
• rs377003436
• NM_032854.4:c.1387A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_032854.4(CORO6):​c.1387A>G​(p.Met463Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000405 in 1,551,846 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M463T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00056 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00039 (2 hom.)
• Consequence: CORO6 NM_032854.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.07
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014758527).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032854.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORO6	NM_032854.4	MANE Select	c.1387A>G	p.Met463Val	missense	Exon 11 of 11	NP_116243.2	Q6QEF8-5
	CORO6	NM_001388431.1		c.1387A>G	p.Met463Val	missense	Exon 11 of 11	NP_001375360.1	Q6QEF8-5
	CORO6	NM_001388433.1		c.1384A>G	p.Met462Val	missense	Exon 11 of 11	NP_001375362.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CORO6	ENST00000388767.8	TSL:2 MANE Select	c.1387A>G	p.Met463Val	missense	Exon 11 of 11	ENSP00000373419.3	Q6QEF8-5
	CORO6	ENST00000480954.6	TSL:1	n.*712A>G		non_coding_transcript_exon	Exon 7 of 7	ENSP00000464621.1	J3QSC1
	CORO6	ENST00000480954.6	TSL:1	n.*712A>G		3_prime_UTR	Exon 7 of 7	ENSP00000464621.1	J3QSC1

Frequencies

GnomAD3 genomes AF: 0.000559 AC: 85 AN: 152078 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00379

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: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000376 AC: 57 AN: 151526 AF XY: 0.000358

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00109

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000482

Gnomad OTH exome AF: 0.000697

GnomAD4 exome AF: 0.000388 AC: 543 AN: 1399650 Hom.: 2 Cov.: 32 AF XY: 0.000359 AC XY: 248 AN XY: 690706

African (AFR) AF: 0.0000945 AC: 3 AN: 31762

American (AMR) AF: 0.00100 AC: 36 AN: 35884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 36074

South Asian (SAS) AF: 0.00 AC: 0 AN: 79454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47922

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4760

European-Non Finnish (NFE) AF: 0.000448 AC: 484 AN: 1080622

Other (OTH) AF: 0.000345 AC: 20 AN: 57990

GnomAD4 genome AF: 0.000558 AC: 85 AN: 152196 Hom.: 1 Cov.: 33 AF XY: 0.000739 AC XY: 55 AN XY: 74388

African (AFR) AF: 0.0000241 AC: 1 AN: 41548

American (AMR) AF: 0.00379 AC: 58 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000377 Hom.: 0

Bravo AF: 0.000582

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000237 AC: 2

ExAC AF: 0.000135 AC: 15

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.045
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.10
Sift	Benign	0.19	T
Sift4G	Benign	0.092	T
Polyphen		0.0040	B
Vest4		0.20
MVP		0.67
MPC		0.30
ClinPred		0.028	T
GERP RS		5.1
gMVP		0.055
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs377003436; hg19: chr17-27942782;