9-35660823-G-T

Variant names:

• chr9-35660823-G-T
• rs767373279
• ENST00000327351.6:c.468G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_001195201.2(CCDC107):​c.468G>T​(p.Ter156Tyrext*?) variant causes a stop lost 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC107 NM_001195201.2 stop_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.294

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001195201.2 Downstream stopcodon found after 184 codons.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC107	NM_174923.3	c.488G>T	p.Ser163Ile	missense_variant	Exon 5 of 5	ENST00000426546.7	NP_777583.2
ARHGEF39	NM_032818.3	c.*1164C>A		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.488G>T	p.Ser163Ile	missense_variant	Exon 5 of 5	1	NM_174923.3	ENSP00000414964.2
ARHGEF39	ENST00000378387	c.*1164C>A		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

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.488G>T (p.S163I) alteration is located in exon 5 (coding exon 5) of the CCDC107 gene. This alteration results from a G to T substitution at nucleotide position 488, causing the serine (S) at amino acid position 163 to be replaced by an isoleucine (I). 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	0.21
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.52
DEOGEN2	Benign	0.071	.;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.64	T;T
MetaRNN	Benign	0.092	T;T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.045
Sift	Benign	0.080	T;T
Sift4G	Uncertain	0.045	D;T
Polyphen		0.66	.;P
Vest4		0.34
MutPred		0.18		Loss of disorder (P = 0.0259);Loss of disorder (P = 0.0259);
MVP		0.31
MPC		0.68
ClinPred		0.51	D
GERP RS		-2.8
Varity_R		0.066
gMVP		0.080

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs767373279; hg19: chr9-35660820;