chr9-35660868-C-T

Variant names:

• chr9-35660868-C-T
• rs762343169
• NM_174923.3:c.533C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_174923.3(CCDC107):​c.533C>T​(p.Ser178Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S178S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: CCDC107 NM_174923.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0610
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025439113).
• BP6: Variant 9-35660868-C-T is Benign according to our data. Variant chr9-35660868-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2394946.Status of the report is criteria_provided_single_submitter, 1 stars.

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.533C>T	p.Ser178Leu	missense	Exon 5 of 5	NP_777583.2	Q8WV48-1
	ARHGEF39	NM_032818.3	MANE Select	c.*1119G>A		3_prime_UTR	Exon 9 of 9	NP_116207.2	Q8N4T4-1
	CCDC107	NM_001195217.2		c.*85C>T		3_prime_UTR	Exon 5 of 5	NP_001182146.1	Q8WV48-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC107	ENST00000426546.7	TSL:1 MANE Select	c.533C>T	p.Ser178Leu	missense	Exon 5 of 5	ENSP00000414964.2	Q8WV48-1
	ARHGEF39	ENST00000378387.4	TSL:1 MANE Select	c.*1119G>A		3_prime_UTR	Exon 9 of 9	ENSP00000367638.3	Q8N4T4-1
	CCDC107	ENST00000378409.7	TSL:1	c.523+10C>T		intron	N/A	ENSP00000367665.3	Q8WV48-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250614 AF XY: 0.00000738

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: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000246 AC: 36 AN: 1461848 Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 727230

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1112010

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.053
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	11
DANN	Benign	0.72
DEOGEN2	Benign	0.00049	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0035	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.061
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.029
Sift	Benign	1.0	T
Sift4G	Benign	0.68	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.18		Loss of glycosylation at S178 (P = 0.003)
MVP		0.048
MPC		0.21
ClinPred		0.017	T
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.018
gMVP		0.011
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs762343169; hg19: chr9-35660865; COSMIC: COSV58396912; COSMIC: COSV58396912;