X-49064509-G-A

Variant names:

• chrX-49064509-G-A
• rs1557080491
• NM_001163321.4:c.569G>A

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.569G>A​(p.Arg190Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000934 in 1,070,756 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. 13/20 in silico tools predict 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. R190T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.3e-7 (0 hom. 1 hem.)
• Consequence: CCDC120 NM_001163321.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• 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=0.13730839).

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.569G>A	p.Arg190Lys	missense	Exon 6 of 11	NP_001156793.2	Q96HB5-4
	CCDC120	NM_001163322.2		c.428G>A	p.Arg143Lys	missense	Exon 6 of 11	NP_001156794.1	Q96HB5-5
	CCDC120	NM_001271835.1		c.464G>A	p.Arg155Lys	missense	Exon 6 of 10	NP_001258764.1	Q96HB5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC120	ENST00000603986.6	TSL:2 MANE Select	c.569G>A	p.Arg190Lys	missense	Exon 6 of 11	ENSP00000474071.1	Q96HB5-4
	CCDC120	ENST00000606812.5	TSL:1	c.464G>A	p.Arg155Lys	missense	Exon 6 of 10	ENSP00000475676.1	Q96HB5-1
	CCDC120	ENST00000603906.2	TSL:2	c.428G>A	p.Arg143Lys	missense	Exon 6 of 11	ENSP00000474713.2	Q96HB5-5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.34e-7 AC: 1 AN: 1070756 Hom.: 0 Cov.: 32 AF XY: 0.00000287 AC XY: 1 AN XY: 348664

African (AFR) AF: 0.00 AC: 0 AN: 25658

American (AMR) AF: 0.00 AC: 0 AN: 31136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18888

East Asian (EAS) AF: 0.00 AC: 0 AN: 28435

South Asian (SAS) AF: 0.0000196 AC: 1 AN: 50947

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3635

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 828733

Other (OTH) AF: 0.00 AC: 0 AN: 44964

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.44	N
PhyloP100		2.2
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.13
Sift	Benign	0.71	T
Sift4G	Benign	0.30	T
Polyphen		0.84	P
Vest4		0.26
MutPred		0.30		Gain of ubiquitination at R155 (P = 0.0155)
MVP		0.44
ClinPred		0.32	T
GERP RS		3.5
Varity_R		0.11
gMVP		0.57
Mutation Taster		=99/1	polymorphism

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: rs1557080491; hg19: chrX-48922040;