chr17-29615803-C-T

Variant names:

• chr17-29615803-C-T
• rs772136445
• NM_032854.4:c.1348G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032854.4(CORO6):​c.1348G>A​(p.Val450Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,416,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V450L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: CORO6 NM_032854.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.12
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35518265).

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.1348G>A	p.Val450Met	missense	Exon 11 of 11	NP_116243.2	Q6QEF8-5
	CORO6	NM_001388431.1		c.1348G>A	p.Val450Met	missense	Exon 11 of 11	NP_001375360.1	Q6QEF8-5
	CORO6	NM_001388433.1		c.1345G>A	p.Val449Met	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.1348G>A	p.Val450Met	missense	Exon 11 of 11	ENSP00000373419.3	Q6QEF8-5
	CORO6	ENST00000480954.6	TSL:1	n.*673G>A		non_coding_transcript_exon	Exon 7 of 7	ENSP00000464621.1	J3QSC1
	CORO6	ENST00000480954.6	TSL:1	n.*673G>A		3_prime_UTR	Exon 7 of 7	ENSP00000464621.1	J3QSC1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000205 AC: 29 AN: 1416376 Hom.: 0 Cov.: 32 AF XY: 0.0000186 AC XY: 13 AN XY: 700452

African (AFR) AF: 0.00 AC: 0 AN: 32552

American (AMR) AF: 0.00 AC: 0 AN: 37824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25352

East Asian (EAS) AF: 0.00 AC: 0 AN: 37364

South Asian (SAS) AF: 0.00 AC: 0 AN: 80844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48664

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5356

European-Non Finnish (NFE) AF: 0.0000266 AC: 29 AN: 1089810

Other (OTH) AF: 0.00 AC: 0 AN: 58610

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Breast ductal adenocarcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		6.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.19
Sift	Benign	0.047	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.34	B
Vest4		0.43
MutPred		0.35		Gain of disorder (P = 0.0498)
MVP		0.85
MPC		0.56
ClinPred		0.94	D
GERP RS		5.2
gMVP		0.47
Mutation Taster		=49/51	disease causing

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: rs772136445; hg19: chr17-27942821;