Variant 22-28773006-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The ENST00000249064.9(CCDC117):c.157A>G(p.Ser53Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,167,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

CCDC117
ENST00000249064.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.826

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.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity CC117_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062037528).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCDC117	NM_173510.4 linkuse as main transcript	c.157A>G	p.Ser53Gly	missense_variant	1/5	ENST00000249064.9	NP_775781.1
CCDC117	NM_001284263.2 linkuse as main transcript	c.157A>G	p.Ser53Gly	missense_variant	1/4		NP_001271192.1
CCDC117	NM_001284264.2 linkuse as main transcript	c.157A>G	p.Ser53Gly	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.157A>G	p.Ser53Gly	missense_variant	1/5	1	NM_173510.4	ENSP00000249064	P1	Q8IWD4-1

Frequencies

GnomAD3 genomes

AF:

0.0000201

AC:

AN:

149160

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000448

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000304

AC:

AN:

1018608

Hom.:

Cov.:

AF XY:

0.0000313

AC XY:

AN XY:

479112

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000319

Gnomad4 OTH exome

AF:

0.0000763

GnomAD4 genome

AF:

0.0000201

AC:

AN:

149278

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72852

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000448

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

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 21, 2023

The c.157A>G (p.S53G) alteration is located in exon 1 (coding exon 1) of the CCDC117 gene. This alteration results from a A to G substitution at nucleotide position 157, causing the serine (S) at amino acid position 53 to be replaced by a glycine (G). 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

0.073

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.5

DANN

Benign

0.97

DEOGEN2

Benign

0.013

T;.;.;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.62

T;T;T;T

M_CAP

Benign

0.073

MetaRNN

Benign

0.062

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;N;.

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.040

N;N;N;N

REVEL

Benign

0.016

Sift

Benign

0.11

T;T;T;T

Sift4G

Benign

0.53

T;T;T;T

Polyphen

0.030

B;.;.;.

Vest4

0.073

MutPred

0.16

Loss of glycosylation at S53 (P = 0.0046);Loss of glycosylation at S53 (P = 0.0046);Loss of glycosylation at S53 (P = 0.0046);Loss of glycosylation at S53 (P = 0.0046);

MVP

0.068

MPC

0.0073

ClinPred

0.14

GERP RS

1.9

Varity_R

0.052

gMVP

0.097

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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