Genetic Variant CCDC120:p.Gly40Ser (chrX-49062289-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001163321.4(CCDC120):c.118G>A(p.Gly40Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000024 in 1,208,928 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000025 ( 0 hom. 6 hem. )

Consequence

CCDC120
NM_001163321.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.29

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20617336).

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.118G>A	p.Gly40Ser	missense	Exon 3 of 11	NP_001156793.2	Q96HB5-4
CCDC120	NM_001271835.1		c.13G>A	p.Gly5Ser	missense	Exon 3 of 10	NP_001258764.1	Q96HB5-1
CCDC120	NM_001271836.2		c.13G>A	p.Gly5Ser	missense	Exon 3 of 10	NP_001258765.1	Q96HB5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC120	ENST00000603986.6	TSL:2 MANE Select	c.118G>A	p.Gly40Ser	missense	Exon 3 of 11	ENSP00000474071.1	Q96HB5-4
CCDC120	ENST00000606812.5	TSL:1	c.13G>A	p.Gly5Ser	missense	Exon 3 of 10	ENSP00000475676.1	Q96HB5-1
CCDC120	ENST00000496529.6	TSL:2	c.13G>A	p.Gly5Ser	missense	Exon 3 of 10	ENSP00000474761.1	Q96HB5-1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

112002

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000222

AC:

AN:

179911

AF XY:

0.0000155

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000499

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1096926

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

362354

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26399

American (AMR)

AF:

0.00

AC:

AN:

35110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19270

East Asian (EAS)

AF:

0.00

AC:

AN:

30190

South Asian (SAS)

AF:

0.00

AC:

AN:

53814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40471

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

841491

Other (OTH)

AF:

0.0000217

AC:

AN:

46046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.0000179

AC:

AN:

112002

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30811

American (AMR)

AF:

0.00

AC:

AN:

10583

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3595

South Asian (SAS)

AF:

0.00

AC:

AN:

2698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000376

AC:

AN:

53125

Other (OTH)

AF:

0.00

AC:

AN:

1505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.0000113

ExAC

AF:

0.0000412

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

Uncertain

0.40

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.44

M_CAP

Benign

0.015

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.83

PhyloP100

4.3

PROVEAN

Benign

-1.1

REVEL

Benign

0.20

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.053

Vest4

0.43

MutPred

0.29

Loss of helix (P = 0.0123)

MVP

0.51

ClinPred

0.38

GERP RS

4.6

Varity_R

0.26

Mutation Taster

=47/53

disease causing

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over