chr9-35660573-G-C

Position:

• chr9-35660573-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000426546.7(CCDC107):​c.336G>C​(p.Gln112His) 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. 14/21 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 ENST00000426546.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30

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

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=0.2501871).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC107	NM_174923.3	c.336G>C	p.Gln112His	missense_variant	4/5	ENST00000426546.7	NP_777583.2
ARHGEF39	NM_032818.3	c.*1414C>G		3_prime_UTR_variant	9/9	ENST00000378387.4	NP_116207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC107	ENST00000426546.7	c.336G>C	p.Gln112His	missense_variant	4/5	1	NM_174923.3	ENSP00000414964	A2
ARHGEF39	ENST00000378387.4	c.*1414C>G		3_prime_UTR_variant	9/9	1	NM_032818.3	ENSP00000367638	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.336G>C (p.Q112H) alteration is located in exon 4 (coding exon 4) of the CCDC107 gene. This alteration results from a G to C substitution at nucleotide position 336, causing the glutamine (Q) at amino acid position 112 to be replaced by a histidine (H). 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	0.27
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.11	.;.;T;T;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.61	T;T;T;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.25	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.3	L;L;.;L;L
MutationTaster	Benign	1.0	D;D;D;D;N;N;N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D
REVEL	Benign	0.12
Sift	Benign	0.053	T;D;D;D;D
Sift4G	Benign	0.099	T;T;T;T;T
Polyphen		1.0, 1.0	.;.;.;D;D
Vest4		0.44
MutPred		0.18		Loss of stability (P = 0.3159);Loss of stability (P = 0.3159);Loss of stability (P = 0.3159);Loss of stability (P = 0.3159);Loss of stability (P = 0.3159);
MVP		0.45
MPC		0.84
ClinPred		0.94	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.50

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-35660570;