Genetic Variant NM_174923.3:c.46G>T (chr9-35658425-G-T) – 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>T(p.Val16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V16A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCDC107
NM_174923.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.846

Publications

1 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: 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=0.13988313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC107	NM_174923.3 link	c.46G>T	p.Val16Leu	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>T	p.Val16Leu	missense_variant	Exon 1 of 5	1	NM_174923.3	ENSP00000414964.2		Q8WV48-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1304810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

641482

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:

0.00

AC:

AN:

1035492

Other (OTH)

AF:

0.00

AC:

AN:

53902

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.040

.;.;T;T;.;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.77

T;T;T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.14

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;.;L;L;L

PhyloP100

0.85

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.6

N;N;N;N;N;D

REVEL

Benign

0.030

Sift

Benign

0.036

D;D;D;D;D;D

Sift4G

Uncertain

0.053

T;T;T;D;D;T

Polyphen

0.040, 0.015

.;.;.;B;B;B

Vest4

0.24

MutPred

0.32

Gain of helix (P = 0.0861);Gain of helix (P = 0.0861);Gain of helix (P = 0.0861);Gain of helix (P = 0.0861);Gain of helix (P = 0.0861);Gain of helix (P = 0.0861);

MVP

0.25

MPC

0.24

ClinPred

0.16

GERP RS

1.3

PromoterAI

-0.018

Neutral

(source)

Varity_R

0.16

gMVP

0.38

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

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

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