Genetic Variant CCDC120:p.Pro130Ala (chrX-49063960-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001163321.4(CCDC120):c.388C>G(p.Pro130Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,094,887 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P130Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

CCDC120
NM_001163321.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.399

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

osteopetrosis
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

CCDC120 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034323573).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163321.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC120	NM_001163321.4	MANE Select	c.388C>G	p.Pro130Ala	missense	Exon 5 of 11	NP_001156793.2	Q96HB5-4
CCDC120	NM_001163322.2		c.247C>G	p.Pro83Ala	missense	Exon 5 of 11	NP_001156794.1	Q96HB5-5
CCDC120	NM_001271835.1		c.283C>G	p.Pro95Ala	missense	Exon 5 of 10	NP_001258764.1	Q96HB5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC120	ENST00000603986.6	TSL:2 MANE Select	c.388C>G	p.Pro130Ala	missense	Exon 5 of 11	ENSP00000474071.1	Q96HB5-4
CCDC120	ENST00000606812.5	TSL:1	c.283C>G	p.Pro95Ala	missense	Exon 5 of 10	ENSP00000475676.1	Q96HB5-1
CCDC120	ENST00000603906.2	TSL:2	c.247C>G	p.Pro83Ala	missense	Exon 5 of 11	ENSP00000474713.2	Q96HB5-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.13e-7

AC:

AN:

1094887

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

360607

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26336

American (AMR)

AF:

0.00

AC:

AN:

34842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19244

East Asian (EAS)

AF:

0.00

AC:

AN:

30077

South Asian (SAS)

AF:

0.00

AC:

AN:

53520

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40333

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4125

European-Non Finnish (NFE)

AF:

0.00000119

AC:

AN:

840492

Other (OTH)

AF:

0.00

AC:

AN:

45918

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.4

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0060

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.64

M_CAP

Benign

0.0029

MetaRNN

Benign

0.034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

0.40

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.18

REVEL

Benign

0.022

Sift

Benign

0.34

Sift4G

Benign

0.34

Polyphen

0.0010

Vest4

0.30

MutPred

0.14

Loss of glycosylation at P95 (P = 0.0127)

MVP

0.043

ClinPred

0.13

GERP RS

2.2

Varity_R

0.026

gMVP

0.50

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over