Genetic Variant CCDC107:p.Val16Met (chr9-35658425-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174923.3(CCDC107):c.46G>A(p.Val16Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000766 in 1,304,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. V16L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

CCDC107
NM_174923.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.846

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21709502).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC107	NM_174923.3 link	c.46G>A	p.Val16Met	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.46G>A	p.Val16Met	missense_variant	Exon 1 of 5	1	NM_174923.3	ENSP00000414964.2		Q8WV48-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.66e-7

AC:

AN:

1304810

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

641482

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

26720

American (AMR)

AF:

0.00

AC:

AN:

25618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22314

East Asian (EAS)

AF:

0.00

AC:

AN:

28954

South Asian (SAS)

AF:

0.00

AC:

AN:

67946

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5364

European-Non Finnish (NFE)

AF:

9.66e-7

AC:

AN:

1035492

Other (OTH)

AF:

0.00

AC:

AN:

53902

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.038

.;.;T;T;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.74

T;T;T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.22

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;.;L;L;L

PhyloP100

0.85

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.5

N;N;N;N;N;D

REVEL

Benign

0.093

Sift

Benign

0.095

T;T;T;T;T;T

Sift4G

Benign

0.12

T;T;T;T;T;T

Polyphen

0.98, 0.94

.;.;.;D;P;D

Vest4

0.28

MutPred

0.26

Loss of catalytic residue at V16 (P = 0.0083);Loss of catalytic residue at V16 (P = 0.0083);Loss of catalytic residue at V16 (P = 0.0083);Loss of catalytic residue at V16 (P = 0.0083);Loss of catalytic residue at V16 (P = 0.0083);Loss of catalytic residue at V16 (P = 0.0083);

MVP

0.35

MPC

0.24

ClinPred

0.52

GERP RS

1.3

PromoterAI

0.0025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.088

gMVP

0.42

Mutation Taster

=94/6

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over