chr9-35658680-C-G

Position:

• chr9-35658680-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_174923.3(CCDC107):​c.211C>G​(p.Leu71Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,966 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: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CCDC107 NM_174923.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.408

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3059964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC107	NM_174923.3	c.211C>G	p.Leu71Val	missense_variant	2/5	ENST00000426546.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC107	ENST00000426546.7	c.211C>G	p.Leu71Val	missense_variant	2/5	1	NM_174923.3	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416966 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 705088

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.12e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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 08, 2023

The c.211C>G (p.L71V) alteration is located in exon 2 (coding exon 2) of the CCDC107 gene. This alteration results from a C to G substitution at nucleotide position 211, causing the leucine (L) at amino acid position 71 to be replaced by a valine (V). 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	0.16
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.80	T;T;T;T;T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.31	T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.7	L;L;.;L;L;L
MutationTaster	Benign	0.78	N;N;N;N;N;N
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.3	N;N;N;N;N;D
REVEL	Benign	0.20
Sift	Uncertain	0.014	D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		1.0	.;.;.;D;D;D
Vest4		0.53
MutPred		0.36		Gain of phosphorylation at Y72 (P = 0.1215);Gain of phosphorylation at Y72 (P = 0.1215);Gain of phosphorylation at Y72 (P = 0.1215);Gain of phosphorylation at Y72 (P = 0.1215);Gain of phosphorylation at Y72 (P = 0.1215);Gain of phosphorylation at Y72 (P = 0.1215);
MVP		0.35
MPC		0.85
ClinPred		0.95	D
GERP RS		2.1
Varity_R		0.22
gMVP		0.51

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-35658677;