Genetic Variant NM_174923.3:c.409C>A (chr9-35660646-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174923.3(CCDC107):c.409C>A(p.Arg137Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CCDC107
NM_174923.3 missense, splice_region

Scores

Splicing: ADA: 0.0002600

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.977

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2243909).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC107	NM_174923.3 link	c.409C>A	p.Arg137Ser	missense_variant, splice_region_variant	Exon 4 of 5	ENST00000426546.7	NP_777583.2	Q8WV48-1
ARHGEF39	NM_032818.3 link	c.*1341G>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000378387.4	NP_116207.2	Q8N4T4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC107	ENST00000426546.7 link	c.409C>A	p.Arg137Ser	missense_variant, splice_region_variant	Exon 4 of 5	1	NM_174923.3	ENSP00000414964.2		Q8WV48-1
ARHGEF39	ENST00000378387 link	c.*1341G>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_032818.3	ENSP00000367638.3		Q8N4T4-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251438

Hom.:

AF XY:

0.0000441

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000330

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.027

.;T;.

Eigen

Benign

-0.089

Eigen_PC

Benign

-0.036

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;L

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.14

T;T;D

Sift4G

Benign

0.064

T;T;D

Polyphen

0.88, 0.67

.;P;P

Vest4

0.66

MutPred

0.33

Gain of disorder (P = 0.1306);Gain of disorder (P = 0.1306);Gain of disorder (P = 0.1306);

MVP

0.42

MPC

0.34

ClinPred

0.14

GERP RS

3.1

Varity_R

0.12

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00026

dbscSNV1_RF

Benign

0.094

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over