Variant 22-28772943-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000249064.9(CCDC117):c.94T>C(p.Phe32Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000222 in 1,218,268 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: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CCDC117
ENST00000249064.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66

Variant links:

Genes affected

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

CCDC117 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.11170408).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCDC117	NM_173510.4 linkuse as main transcript	c.94T>C	p.Phe32Leu	missense_variant	1/5	ENST00000249064.9	NP_775781.1
CCDC117	NM_001284263.2 linkuse as main transcript	c.94T>C	p.Phe32Leu	missense_variant	1/4		NP_001271192.1
CCDC117	NM_001284264.2 linkuse as main transcript	c.94T>C	p.Phe32Leu	missense_variant	1/4		NP_001271193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC117	ENST00000249064.9 linkuse as main transcript	c.94T>C	p.Phe32Leu	missense_variant	1/5	1	NM_173510.4	ENSP00000249064	P1	Q8IWD4-1

Frequencies

GnomAD3 genomes

AF:

0.0000725

AC:

AN:

151622

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00213

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1066538

Hom.:

Cov.:

AF XY:

0.00000991

AC XY:

AN XY:

504556

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000599

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000236

GnomAD4 genome

AF:

0.0000725

AC:

AN:

151730

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00214

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

The c.94T>C (p.F32L) alteration is located in exon 1 (coding exon 1) of the CCDC117 gene. This alteration results from a T to C substitution at nucleotide position 94, causing the phenylalanine (F) at amino acid position 32 to be replaced by a leucine (L). 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

Pathogenic

0.81

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

T;.;.;.

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.61

T;T;T;T

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N;N;.

MutationTaster

Benign

0.50

D;D;N

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.087

Sift

Uncertain

0.028

D;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.93

P;.;.;.

Vest4

0.34

MutPred

0.13

Loss of methylation at R30 (P = 0.1402);Loss of methylation at R30 (P = 0.1402);Loss of methylation at R30 (P = 0.1402);Loss of methylation at R30 (P = 0.1402);

MVP

0.14

MPC

0.020

ClinPred

0.74

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.29

gMVP

0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over