Variant 22-28773018-A-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 NM_173510.4(CCDC117):c.169A>C(p.Ser57Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,130,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

CCDC117
NM_173510.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

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=0.07780254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCDC117	NM_173510.4 linkuse as main transcript	c.169A>C	p.Ser57Arg	missense_variant	1/5	ENST00000249064.9
CCDC117	NM_001284263.2 linkuse as main transcript	c.169A>C	p.Ser57Arg	missense_variant	1/4
CCDC117	NM_001284264.2 linkuse as main transcript	c.169A>C	p.Ser57Arg	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC117	ENST00000249064.9 linkuse as main transcript	c.169A>C	p.Ser57Arg	missense_variant	1/5	1	NM_173510.4	P1	Q8IWD4-1

Frequencies

GnomAD3 genomes

AF:

0.000227

AC:

AN:

145662

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000717

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000274

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.0000213

AC:

AN:

985086

Hom.:

Cov.:

AF XY:

0.0000195

AC XY:

AN XY:

461964

show subpopulations

Gnomad4 AFR exome

AF:

0.000978

Gnomad4 AMR exome

AF:

0.000192

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

AF:

0.000227

AC:

AN:

145662

Hom.:

Cov.:

AF XY:

0.000169

AC XY:

AN XY:

70988

show subpopulations

Gnomad4 AFR

AF:

0.000717

Gnomad4 AMR

AF:

0.000274

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000261

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

Aug 09, 2021

The c.169A>C (p.S57R) alteration is located in exon 1 (coding exon 1) of the CCDC117 gene. This alteration results from a A to C substitution at nucleotide position 169, causing the serine (S) at amino acid position 57 to be replaced by an arginine (R). 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

0.22

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.43

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.029

T;.;.;.

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.64

T;T;T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.078

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N;N;.

MutationTaster

Benign

0.86

N;N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Benign

0.039

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.38

T;T;T;T

Polyphen

0.0040

B;.;.;.

Vest4

0.11

MutPred

0.21

Gain of methylation at S57 (P = 0.0048);Gain of methylation at S57 (P = 0.0048);Gain of methylation at S57 (P = 0.0048);Gain of methylation at S57 (P = 0.0048);

MVP

0.043

MPC

0.030

ClinPred

0.69

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.15

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