Genetic Variant NM_174923.3:c.229G>A (chr9-35658698-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.229G>A(p.Ala77Thr) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

Uncertain significance criteria provided, single submitter U:1

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=0.13103426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC107	NM_174923.3 link	c.229G>A	p.Ala77Thr	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>A	p.Ala77Thr	missense_variant	Exon 2 of 5	1	NM_174923.3	ENSP00000414964.2		Q8WV48-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000519

AC:

AN:

192520

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000115

Gnomad OTH exome

AF:

0.00

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:

0.00

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:

9.14e-7

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 01, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.229G>A (p.A77T) alteration is located in exon 2 (coding exon 2) of the CCDC107 gene. This alteration results from a G to A substitution at nucleotide position 229, causing the alanine (A) at amino acid position 77 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

.;.;T;T;.;.

Eigen

Benign

-0.18

Eigen_PC

Benign

0.023

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.63

T;T;T;T;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.13

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.;N;N;N

PhyloP100

1.7

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.85

N;N;N;N;N;N

REVEL

Benign

0.032

Sift

Benign

0.27

T;T;T;T;T;D

Sift4G

Uncertain

0.036

D;D;D;D;D;D

Polyphen

0.0030, 0.0020

.;.;.;B;B;B

Vest4

0.25

MutPred

0.27

Gain of phosphorylation at A77 (P = 0.0926);Gain of phosphorylation at A77 (P = 0.0926);Gain of phosphorylation at A77 (P = 0.0926);Gain of phosphorylation at A77 (P = 0.0926);Gain of phosphorylation at A77 (P = 0.0926);Gain of phosphorylation at A77 (P = 0.0926);

MVP

0.29

MPC

0.25

ClinPred

0.38

GERP RS

4.2

PromoterAI

0.039

Neutral

(source)

Varity_R

0.17

gMVP

0.44

Mutation Taster

=99/1

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over