Genetic Variant CCDC120:p.Pro171Leu (chrX-49064452-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001163321.4(CCDC120):c.512C>T(p.Pro171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,179,055 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 55 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 7 hem., cov: 24)

Exomes 𝑓: 0.00016 ( 0 hom. 48 hem. )

Consequence

CCDC120
NM_001163321.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.37

Variant links:

Genes affected

CCDC120 (HGNC:28910): (coiled-coil domain containing 120) This gene encodes a protein that contains a coiled-coil domain. Several alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

CCDC120 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008667171).

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC120	NM_001163321.4 link	c.512C>T	p.Pro171Leu	missense_variant	Exon 6 of 11	ENST00000603986.6	NP_001156793.2	Q96HB5-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC120	ENST00000603986.6 link	c.512C>T	p.Pro171Leu	missense_variant	Exon 6 of 11	2	NM_001163321.4	ENSP00000474071.1		Q96HB5-4

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

112504

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

34682

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:

0.000641

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000151

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000155

AC:

AN:

122499

Hom.:

AF XY:

0.000101

AC XY:

AN XY:

39439

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:

0.00132

Gnomad NFE exome

AF:

0.0000823

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000156

AC:

166

AN:

1066551

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

AN XY:

347423

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:

0.000744

Gnomad4 NFE exome

AF:

0.000153

Gnomad4 OTH exome

AF:

0.000245

GnomAD4 genome

AF:

0.000107

AC:

AN:

112504

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

34682

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:

0.000641

Gnomad4 NFE

AF:

0.000151

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000442

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.407C>T (p.P136L) alteration is located in exon 6 (coding exon 4) of the CCDC120 gene. This alteration results from a C to T substitution at nucleotide position 407, causing the proline (P) at amino acid position 136 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

Benign

0.25

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;T;.;.

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

.;.;D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.0087

T;T;T;T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.1

M;M;M;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-6.4

.;.;.;.;D

REVEL

Benign

0.16

Sift

Uncertain

0.0010

.;.;.;.;D

Sift4G

Uncertain

0.026

D;D;D;D;D

Polyphen

1.0

D;D;D;.;.

Vest4

0.41

MutPred

0.27

Gain of helix (P = 0.005);Gain of helix (P = 0.005);Gain of helix (P = 0.005);.;.;

MVP

0.27

ClinPred

0.49

GERP RS

4.8

Varity_R

0.73

gMVP

0.66

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