Genetic Variant CCDC107:p.Ala77Pro (chr9-35658698-G-C) – 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.229G>C(p.Ala77Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,413,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A77T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CCDC107
NM_174923.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

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:

ARHGEF39 (HGNC:25909): (Rho guanine nucleotide exchange factor 39) Predicted to enable guanyl-nucleotide exchange factor activity. Involved in positive regulation of cell migration. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARHGEF39 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=0.18373561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC107	NM_174923.3 link	c.229G>C	p.Ala77Pro	missense_variant	Exon 2 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.229G>C	p.Ala77Pro	missense_variant	Exon 2 of 5	1	NM_174923.3	ENSP00000414964.2		Q8WV48-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1413780

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

703256

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30036

American (AMR)

AF:

0.00

AC:

AN:

40788

Ashkenazi Jewish (ASJ)

AF:

0.0000400

AC:

AN:

25016

East Asian (EAS)

AF:

0.00

AC:

AN:

35228

South Asian (SAS)

AF:

0.00

AC:

AN:

83556

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4462

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1094134

Other (OTH)

AF:

0.00

AC:

AN:

58558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Pathogenic

0.74

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;.;T;T;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

0.056

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.59

T;T;T;T;T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.18

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;.;N;N;N

PhyloP100

1.7

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.4

N;N;N;N;N;N

REVEL

Benign

0.043

Sift

Benign

0.20

T;T;T;T;T;D

Sift4G

Uncertain

0.015

D;D;D;D;D;D

Polyphen

0.10

.;.;.;B;B;B

Vest4

0.40

MutPred

0.44

Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);

MVP

0.37

MPC

0.54

ClinPred

0.65

GERP RS

4.2

PromoterAI

0.0072

Neutral

(source)

Varity_R

0.71

gMVP

0.71

Mutation Taster

=98/2

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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9-35658698-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over