Variant 13-43859760-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144974.5(CCDC122):c.467G>A(p.Arg156Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000557 in 1,597,942 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

CCDC122
NM_144974.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.32

Variant links:

Genes affected

CCDC122 (HGNC:26478): (coiled-coil domain containing 122) This gene encodes a protein that contains a coiled-coil domain. Naturally occurring mutations in this gene are associated with leprosy. [provided by RefSeq, Apr 2017]

CCDC122 links:

CCDC122 (HGNC:):

CCDC122 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040684253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC122	NM_144974.5 linkuse as main transcript	c.467G>A	p.Arg156Gln	missense_variant	5/7	ENST00000444614.8	NP_659411.2	Q5T0U0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC122	ENST00000444614.8 linkuse as main transcript	c.467G>A	p.Arg156Gln	missense_variant	5/7	5	NM_144974.5	ENSP00000407763.2	Q5T0U0-1
CCDC122	ENST00000470137.5 linkuse as main transcript	n.396G>A		non_coding_transcript_exon_variant	2/4	5
CCDC122	ENST00000476570.2 linkuse as main transcript	n.727G>A		non_coding_transcript_exon_variant	5/7	5

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000884

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000594

AC:

AN:

235734

Hom.:

AF XY:

0.0000943

AC XY:

AN XY:

127314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000128

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000567

AC:

AN:

1445922

Hom.:

Cov.:

AF XY:

0.0000612

AC XY:

AN XY:

718658

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000650

Gnomad4 OTH exome

AF:

0.000134

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152020

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000884

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000412

AC:

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 27, 2024

The c.467G>A (p.R156Q) alteration is located in exon 5 (coding exon 3) of the CCDC122 gene. This alteration results from a G to A substitution at nucleotide position 467, causing the arginine (R) at amino acid position 156 to be replaced by a glutamine (Q). 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

0.065

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.17

DANN

Benign

0.77

DEOGEN2

Benign

0.025

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.67

M_CAP

Benign

0.022

MetaRNN

Benign

0.041

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.84

REVEL

Benign

0.13

Sift

Benign

0.081

Sift4G

Benign

0.16

Polyphen

0.028

Vest4

0.084

MutPred

0.35

Loss of MoRF binding (P = 0.0255);

MVP

0.30

MPC

0.037

ClinPred

0.23

GERP RS

-5.8

Varity_R

0.043

gMVP

0.28

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