17-29615803-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CORO6	NM_032854.4	c.1348G>A	p.Val450Met	missense_variant	Exon 11 of 11	ENST00000388767.8	NP_116243.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORO6	ENST00000388767.8	c.1348G>A	p.Val450Met	missense_variant	Exon 11 of 11	2	NM_032854.4	ENSP00000373419.3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000266

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Breast ductal adenocarcinoma Uncertain:1

Jul 20, 2015

Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;.;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.7	M;M;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.3	N;.;.;.
REVEL	Benign	0.19
Sift	Benign	0.047	D;.;.;.
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.34	B;B;.;.
Vest4		0.43
MutPred		0.35		Gain of disorder (P = 0.0498);Gain of disorder (P = 0.0498);.;.;
MVP		0.85
MPC		0.56
ClinPred		0.94	D
GERP RS		5.2
gMVP		0.47

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: rs772136445; hg19: chr17-27942821;