9-35658642-G-C

Variant names:

• chr9-35658642-G-C
• rs1191691731
• NM_174923.3:c.173G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174923.3(CCDC107):​c.173G>C​(p.Arg58Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000509 in 1,571,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: CCDC107 NM_174923.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.633
• Publications: 0 publications found

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]

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]

ACMG classification

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=0.26329792).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174923.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC107	NM_174923.3	MANE Select	c.173G>C	p.Arg58Pro	missense	Exon 2 of 5	NP_777583.2	Q8WV48-1
	CCDC107	NM_001195200.2		c.173G>C	p.Arg58Pro	missense	Exon 2 of 6	NP_001182129.1	Q8WV48-5
	CCDC107	NM_001195201.2		c.173G>C	p.Arg58Pro	missense	Exon 2 of 6	NP_001182130.1	Q8WV48-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC107	ENST00000426546.7	TSL:1 MANE Select	c.173G>C	p.Arg58Pro	missense	Exon 2 of 5	ENSP00000414964.2	Q8WV48-1
	CCDC107	ENST00000378409.7	TSL:1	c.173G>C	p.Arg58Pro	missense	Exon 2 of 6	ENSP00000367665.3	Q8WV48-5
	CCDC107	ENST00000327351.6	TSL:1	c.173G>C	p.Arg58Pro	missense	Exon 2 of 6	ENSP00000330327.2	Q8WV48-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 202598 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000493 AC: 7 AN: 1419042 Hom.: 0 Cov.: 27 AF XY: 0.00000424 AC XY: 3 AN XY: 707112

African (AFR) AF: 0.0000321 AC: 1 AN: 31184

American (AMR) AF: 0.00 AC: 0 AN: 43636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25426

East Asian (EAS) AF: 0.00 AC: 0 AN: 36778

South Asian (SAS) AF: 0.00 AC: 0 AN: 84856

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4180

European-Non Finnish (NFE) AF: 0.00000548 AC: 6 AN: 1094010

Other (OTH) AF: 0.00 AC: 0 AN: 58976

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

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

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	0.0051	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.63
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.15
Sift	Benign	0.067	T
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.43
MutPred		0.46		Loss of MoRF binding (P = 0.003)
MVP		0.45
MPC		0.98
ClinPred		0.98	D
GERP RS		4.2
PromoterAI		0.020	Neutral
Varity_R		0.67
gMVP		0.50
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs1191691731; hg19: chr9-35658639;