rs1823855814

Variant names:

• chr9-35660414-C-G
• rs1823855814
• NM_174923.3:c.272C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_174923.3(CCDC107):​c.272C>G​(p.Thr91Ser) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC107 NM_174923.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.450
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049190074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC107	NM_174923.3	c.272C>G	p.Thr91Ser	missense_variant	Exon 3 of 5	ENST00000426546.7	NP_777583.2
ARHGEF39	NM_032818.3	c.*1573G>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000378387.4	NP_116207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC107	ENST00000426546.7	c.272C>G	p.Thr91Ser	missense_variant	Exon 3 of 5	1	NM_174923.3	ENSP00000414964.2
ARHGEF39	ENST00000378387.4	c.*1573G>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_032818.3	ENSP00000367638.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 23, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.272C>G (p.T91S) alteration is located in exon 3 (coding exon 3) of the CCDC107 gene. This alteration results from a C to G substitution at nucleotide position 272, causing the threonine (T) at amino acid position 91 to be replaced by a serine (S). 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	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	11
DANN	Benign	0.65
DEOGEN2	Benign	0.0075	.;.;T;T;.;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.60	T;T;T;T;T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.049	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;N;.;N;N;N
PhyloP100		0.45
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.18	N;N;N;N;N;N
REVEL	Benign	0.045
Sift	Benign	0.36	T;T;T;T;T;T
Sift4G	Benign	0.14	T;T;T;T;T;T
Polyphen		0.048, 0.026	.;.;.;B;B;B
Vest4		0.21
MutPred		0.12		Gain of disorder (P = 0.0756);Gain of disorder (P = 0.0756);Gain of disorder (P = 0.0756);Gain of disorder (P = 0.0756);Gain of disorder (P = 0.0756);Gain of disorder (P = 0.0756);
MVP		0.14
MPC		0.25
ClinPred		0.053	T
GERP RS		1.6
Varity_R		0.066
gMVP		0.14
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1823855814; hg19: chr9-35660411;