22-28772979-C-T

Variant summary

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

The NM_173510.4(CCDC117):c.130C>T(p.Arg44Trp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC117 NM_173510.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.749

Genes affected

CCDC117 (HGNC:26599): (coiled-coil domain containing 117)

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=0.3348894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC117	NM_173510.4	c.130C>T	p.Arg44Trp	missense_variant	1/5	ENST00000249064.9
CCDC117	NM_001284263.2	c.130C>T	p.Arg44Trp	missense_variant	1/4
CCDC117	NM_001284264.2	c.130C>T	p.Arg44Trp	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC117	ENST00000249064.9	c.130C>T	p.Arg44Trp	missense_variant	1/5	1	NM_173510.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1046834 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 493916

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: 0.00

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

Dec 06, 2022

The c.130C>T (p.R44W) alteration is located in exon 1 (coding exon 1) of the CCDC117 gene. This alteration results from a C to T substitution at nucleotide position 130, causing the arginine (R) at amino acid position 44 to be replaced by a tryptophan (W). 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	0.32
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.040	T;.;.;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;L;L;.
MutationTaster	Benign	0.83	D;D;N
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-2.2	N;N;N;D
REVEL	Benign	0.16
Sift	Uncertain	0.025	D;D;D;D
Sift4G	Benign	0.097	T;T;T;T
Polyphen		1.0	D;.;.;.
Vest4		0.24
MutPred		0.23		Loss of methylation at R44 (P = 0.0281);Loss of methylation at R44 (P = 0.0281);Loss of methylation at R44 (P = 0.0281);Loss of methylation at R44 (P = 0.0281);
MVP		0.082
MPC		0.035
ClinPred		0.95	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.31

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: chr22-29168967;