dbSNP rs781809137: CCDC120:p.Pro130Leu (chrX-49063961-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001163321.4(CCDC120):c.389C>T(p.Pro130Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000332 in 1,205,207 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 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: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000033 ( 0 hom. 6 hem. )

Consequence

CCDC120
NM_001163321.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.410

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008878529).

BS2

High Hemizygotes in GnomAdExome4 at 6 XL gene

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.389C>T	p.Pro130Leu	missense	Exon 5 of 11	NP_001156793.2	Q96HB5-4
CCDC120	NM_001163322.2		c.248C>T	p.Pro83Leu	missense	Exon 5 of 11	NP_001156794.1	Q96HB5-5
CCDC120	NM_001271835.1		c.284C>T	p.Pro95Leu	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.389C>T	p.Pro130Leu	missense	Exon 5 of 11	ENSP00000474071.1	Q96HB5-4
CCDC120	ENST00000606812.5	TSL:1	c.284C>T	p.Pro95Leu	missense	Exon 5 of 10	ENSP00000475676.1	Q96HB5-1
CCDC120	ENST00000603906.2	TSL:2	c.248C>T	p.Pro83Leu	missense	Exon 5 of 11	ENSP00000474713.2	Q96HB5-5

Frequencies

GnomAD3 genomes

AF:

0.0000360

AC:

AN:

111023

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:

0.00113

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000937

AC:

AN:

170814

AF XY:

0.0000519

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000380

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000763

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000237

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1094184

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

360036

show subpopulations

African (AFR)

AF:

0.000114

AC:

AN:

26317

American (AMR)

AF:

0.0000288

AC:

AN:

34750

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19219

East Asian (EAS)

AF:

0.000333

AC:

AN:

30002

South Asian (SAS)

AF:

0.000168

AC:

AN:

53422

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40296

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4124

European-Non Finnish (NFE)

AF:

0.0000107

AC:

AN:

840162

Other (OTH)

AF:

0.0000872

AC:

AN:

45892

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000360

AC:

AN:

111023

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33219

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30460

American (AMR)

AF:

0.00

AC:

AN:

10476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2640

East Asian (EAS)

AF:

0.00113

AC:

AN:

3532

South Asian (SAS)

AF:

0.00

AC:

AN:

2639

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6007

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52863

Other (OTH)

AF:

0.00

AC:

AN:

1486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000907

AC:

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

0.067

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.5

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.0041

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.73

M_CAP

Benign

0.0034

MetaRNN

Benign

0.0089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.90

PhyloP100

0.41

PrimateAI

Benign

0.44

PROVEAN

Benign

0.63

REVEL

Benign

0.030

Sift

Benign

0.35

Sift4G

Uncertain

0.014

Polyphen

0.0

Vest4

0.099

MVP

0.043

ClinPred

0.016

GERP RS

1.3

Varity_R

0.035

gMVP

0.51

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over