17-29615997-C-G

Variant names:

• chr17-29615997-C-G
• rs558798899
• NM_032854.4:c.1241G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032854.4(CORO6):​c.1241G>C​(p.Arg414Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,442 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R414H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CORO6 NM_032854.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1241G>C	p.Arg414Pro	missense	Exon 10 of 11	NP_116243.2	Q6QEF8-5
	CORO6	NM_001388431.1		c.1241G>C	p.Arg414Pro	missense	Exon 10 of 11	NP_001375360.1	Q6QEF8-5
	CORO6	NM_001388433.1		c.1241G>C	p.Arg414Pro	missense	Exon 10 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.1241G>C	p.Arg414Pro	missense	Exon 10 of 11	ENSP00000373419.3	Q6QEF8-5
	CORO6	ENST00000480954.6	TSL:1	n.*569G>C		non_coding_transcript_exon	Exon 6 of 7	ENSP00000464621.1	J3QSC1
	CORO6	ENST00000480954.6	TSL:1	n.*569G>C		3_prime_UTR	Exon 6 of 7	ENSP00000464621.1	J3QSC1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434442 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 710848

African (AFR) AF: 0.00 AC: 0 AN: 33110

American (AMR) AF: 0.00 AC: 0 AN: 41820

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25278

East Asian (EAS) AF: 0.00 AC: 0 AN: 38634

South Asian (SAS) AF: 0.00 AC: 0 AN: 84066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096802

Other (OTH) AF: 0.00 AC: 0 AN: 59148

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Benign	0.83
DEOGEN2	Benign	0.024	T
Eigen	Benign	0.089
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.097	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.4
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.17
Sift	Benign	0.16	T
Sift4G	Benign	0.24	T
Polyphen		0.0010	B
Vest4		0.43
MutPred		0.43		Loss of MoRF binding (P = 0.0051)
MVP		0.80
MPC		0.96
ClinPred		0.72	D
GERP RS		5.2
gMVP		0.49
Mutation Taster		=57/43	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: rs558798899; hg19: chr17-27943015;