10-114132011-T-A

Position:

• chr10-114132011-T-A

Variant summary

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

The NM_018017.4(CCDC186):​c.1829A>T​(p.Gln610Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC186 NM_018017.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03

Genes affected

CCDC186 (HGNC:24349): (coiled-coil domain containing 186) Predicted to enable small GTPase binding activity. Predicted to be involved in vesicle cytoskeletal trafficking. Predicted to act upstream of or within insulin secretion involved in cellular response to glucose stimulus and response to bacterium. Predicted to be located in Golgi apparatus. Predicted to be active in trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

CCDC186 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
CCDC186	NM_018017.4	c.1829A>T	p.Gln610Leu	missense_variant	11/16	ENST00000369287.8	NP_060487.2
CCDC186	NM_001321829.1	c.1829A>T	p.Gln610Leu	missense_variant	12/17		NP_001308758.1
CCDC186	XM_011539915.4	c.1088A>T	p.Gln363Leu	missense_variant	10/15		XP_011538217.1
CCDC186	NR_135815.1	n.2221A>T		non_coding_transcript_exon_variant	12/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC186	ENST00000369287.8	c.1829A>T	p.Gln610Leu	missense_variant	11/16	1	NM_018017.4	ENSP00000358293.3
CCDC186	ENST00000648613.1	c.1829A>T	p.Gln610Leu	missense_variant	12/17			ENSP00000498136.1
CCDC186	ENST00000428953.1	c.713A>T	p.Gln238Leu	missense_variant	6/10	2		ENSP00000415344.1
CCDC186	ENST00000490661.1	n.84A>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2022

The c.1829A>T (p.Q610L) alteration is located in exon 11 (coding exon 10) of the CCDC186 gene. This alteration results from a A to T substitution at nucleotide position 1829, causing the glutamine (Q) at amino acid position 610 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
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.058	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	.;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.74	T
PROVEAN	Uncertain	-3.8	D;.
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D;.
Sift4G	Benign	0.15	T;.
Polyphen		1.0	D;D
Vest4		0.55
MutPred		0.16		Loss of methylation at K615 (P = 0.1355);Loss of methylation at K615 (P = 0.1355);
MVP		0.44
MPC		0.27
ClinPred		0.97	D
GERP RS		5.7
Varity_R		0.42
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-115891770;