X-49062289-G-T

Variant names:

• chrX-49062289-G-T
• rs782450023
• NM_001163321.4:c.118G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001163321.4(CCDC120):​c.118G>T​(p.Gly40Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,096,926 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G40S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: CCDC120 NM_001163321.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22084138).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC120	NM_001163321.4	MANE Select	c.118G>T	p.Gly40Cys	missense	Exon 3 of 11	NP_001156793.2	Q96HB5-4
	CCDC120	NM_001271835.1		c.13G>T	p.Gly5Cys	missense	Exon 3 of 10	NP_001258764.1	Q96HB5-1
	CCDC120	NM_001271836.2		c.13G>T	p.Gly5Cys	missense	Exon 3 of 10	NP_001258765.1	Q96HB5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC120	ENST00000603986.6	TSL:2 MANE Select	c.118G>T	p.Gly40Cys	missense	Exon 3 of 11	ENSP00000474071.1	Q96HB5-4
	CCDC120	ENST00000606812.5	TSL:1	c.13G>T	p.Gly5Cys	missense	Exon 3 of 10	ENSP00000475676.1	Q96HB5-1
	CCDC120	ENST00000496529.6	TSL:2	c.13G>T	p.Gly5Cys	missense	Exon 3 of 10	ENSP00000474761.1	Q96HB5-1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1096926 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 1 AN XY: 362354

African (AFR) AF: 0.00 AC: 0 AN: 26399

American (AMR) AF: 0.00 AC: 0 AN: 35110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19270

East Asian (EAS) AF: 0.00 AC: 0 AN: 30190

South Asian (SAS) AF: 0.0000372 AC: 2 AN: 53814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40471

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841491

Other (OTH) AF: 0.00 AC: 0 AN: 46046

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	33
DANN	Uncertain	1.0
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.51	T
PhyloP100		4.3
PROVEAN	Benign	0.57	N
REVEL	Benign	0.13
Sift	Benign	0.20	T
Sift4G	Benign	0.47	T
Vest4		0.45
MutPred		0.22		Loss of helix (P = 0.0196)
MVP		0.59
ClinPred		0.95	D
GERP RS		4.6
Varity_R		0.75
Mutation Taster		=49/51	disease causing

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

Other links and lift over

dbSNP: rs782450023; hg19: chrX-48919820;