Genetic Variant CCDC107:p.Leu13Met (chr9-35658416-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_174923.3(CCDC107):c.37C>A(p.Leu13Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000829 in 1,447,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

CCDC107
NM_174923.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.333

Publications

0 publications found

Variant links:

Genes affected

CCDC107 (HGNC:28465): (coiled-coil domain containing 107) This gene encodes a membrane protein which contains a coiled-coil domain in the central region. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2013]

CCDC107 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09579167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC107	NM_174923.3 link	c.37C>A	p.Leu13Met	missense_variant	Exon 1 of 5	ENST00000426546.7	NP_777583.2	Q8WV48-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC107	ENST00000426546.7 link	c.37C>A	p.Leu13Met	missense_variant	Exon 1 of 5	1	NM_174923.3	ENSP00000414964.2		Q8WV48-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000609

AC:

AN:

82130

AF XY:

0.0000675

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00136

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000695

AC:

AN:

1295290

Hom.:

Cov.:

AF XY:

0.00000786

AC XY:

AN XY:

636154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26566

American (AMR)

AF:

0.00

AC:

AN:

24750

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21790

East Asian (EAS)

AF:

0.000278

AC:

AN:

28750

South Asian (SAS)

AF:

0.00

AC:

AN:

66314

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37986

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4684

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1031016

Other (OTH)

AF:

0.0000187

AC:

AN:

53434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41572

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000582

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.37C>A (p.L13M) alteration is located in exon 1 (coding exon 1) of the CCDC107 gene. This alteration results from a C to A substitution at nucleotide position 37, causing the leucine (L) at amino acid position 13 to be replaced by a methionine (M). 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

0.19

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.034

.;.;T;T;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.65

T;T;T;T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.096

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

L;L;.;L;L;L

PhyloP100

-0.33

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.65

N;N;N;N;N;N

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0, 1.0

.;.;.;D;D;D

Vest4

0.46

MutPred

0.32

Loss of catalytic residue at L13 (P = 0.0444);Loss of catalytic residue at L13 (P = 0.0444);Loss of catalytic residue at L13 (P = 0.0444);Loss of catalytic residue at L13 (P = 0.0444);Loss of catalytic residue at L13 (P = 0.0444);Loss of catalytic residue at L13 (P = 0.0444);

MVP

0.22

MPC

0.23

ClinPred

0.20

GERP RS

1.3

PromoterAI

-0.20

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.26

gMVP

0.29

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

9-35658416-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over