Variant chr10-114125974-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018017.4(CCDC186):c.2525A>G(p.Asn842Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CCDC186
NM_018017.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.27

Variant links:

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 links:

CCDC186 (HGNC:):

CCDC186 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037702292).

BP6

Variant 10-114125974-T-C is Benign according to our data. Variant chr10-114125974-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2527273.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC186	NM_018017.4 linkuse as main transcript	c.2525A>G	p.Asn842Ser	missense_variant	15/16	ENST00000369287.8	NP_060487.2	Q7Z3E2
CCDC186	NM_001321829.1 linkuse as main transcript	c.2525A>G	p.Asn842Ser	missense_variant	16/17		NP_001308758.1	Q7Z3E2Q496Y1
CCDC186	XM_011539915.4 linkuse as main transcript	c.1784A>G	p.Asn595Ser	missense_variant	14/15		XP_011538217.1
CCDC186	NR_135815.1 linkuse as main transcript	n.3404A>G		non_coding_transcript_exon_variant	15/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC186	ENST00000369287.8 linkuse as main transcript	c.2525A>G	p.Asn842Ser	missense_variant	15/16	1	NM_018017.4	ENSP00000358293.3	Q7Z3E2
CCDC186	ENST00000648613.1 linkuse as main transcript	c.2525A>G	p.Asn842Ser	missense_variant	16/17			ENSP00000498136.1	Q7Z3E2
CCDC186	ENST00000428953.1 linkuse as main transcript	c.1278-748A>G		intron_variant		2		ENSP00000415344.1	H0Y7V5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251170

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135734

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727144

show subpopulations

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000833

Hom.:

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 20, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.20

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-0.95

PROVEAN

Benign

0.27

N;.

REVEL

Benign

0.17

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;.

Polyphen

0.0

B;B

Vest4

0.071

MVP

0.067

MPC

0.21

ClinPred

0.021

GERP RS

3.0

Varity_R

0.046

gMVP

0.036

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over