22-28786247-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_173510.4(CCDC117):c.761C>T(p.Ser254Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,613,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

CCDC117
NM_173510.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.897

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.016626865).

BP6

Variant 22-28786247-C-T is Benign according to our data. Variant chr22-28786247-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3138285.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCDC117	NM_173510.4 linkuse as main transcript	c.761C>T	p.Ser254Leu	missense_variant	5/5	ENST00000249064.9
CCDC117	NM_001284263.2 linkuse as main transcript	c.707C>T	p.Ser236Leu	missense_variant	4/4
CCDC117	NM_001284264.2 linkuse as main transcript	c.536C>T	p.Ser179Leu	missense_variant	4/4
CCDC117	NM_001284265.1 linkuse as main transcript	c.365C>T	p.Ser122Leu	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC117	ENST00000249064.9 linkuse as main transcript	c.761C>T	p.Ser254Leu	missense_variant	5/5	1	NM_173510.4	P1	Q8IWD4-1
CCDC117	ENST00000448492.6 linkuse as main transcript	c.707C>T	p.Ser236Leu	missense_variant	4/4	2			Q8IWD4-3
CCDC117	ENST00000421503.6 linkuse as main transcript	c.536C>T	p.Ser179Leu	missense_variant	4/4	2			Q8IWD4-4

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000954

AC:

AN:

251486

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000721

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 18, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.68

Cadd

Benign

Dann

Benign

0.13

DEOGEN2

Benign

0.026

T;.;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.56

T;T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

N;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.76

N;N;N

REVEL

Benign

0.053

Sift

Benign

0.67

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.063

MutPred

0.18

Gain of sheet (P = 0.0149);.;.;

MVP

0.043

MPC

0.0073

ClinPred

0.025

GERP RS

3.7

Varity_R

0.020

gMVP

0.084

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