NM_001163321.4:c.569G>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001163321.4(CCDC120):​c.569G>C​(p.Arg190Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,070,759 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000019 (0 hom. 0 hem.)
• Consequence: CCDC120 NM_001163321.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26604068).

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>C	p.Arg190Thr	missense	Exon 6 of 11	NP_001156793.2	Q96HB5-4
	CCDC120	NM_001163322.2		c.428G>C	p.Arg143Thr	missense	Exon 6 of 11	NP_001156794.1	Q96HB5-5
	CCDC120	NM_001271835.1		c.464G>C	p.Arg155Thr	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>C	p.Arg190Thr	missense	Exon 6 of 11	ENSP00000474071.1	Q96HB5-4
	CCDC120	ENST00000606812.5	TSL:1	c.464G>C	p.Arg155Thr	missense	Exon 6 of 10	ENSP00000475676.1	Q96HB5-1
	CCDC120	ENST00000603906.2	TSL:2	c.428G>C	p.Arg143Thr	missense	Exon 6 of 11	ENSP00000474713.2	Q96HB5-5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000153 AC: 2 AN: 131003 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000894

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000187 AC: 2 AN: 1070759 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 348667

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

American (AMR) AF: 0.0000642 AC: 2 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: 0.00 AC: 0 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: 828736

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

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.20	T
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.2
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.075	T
Polyphen		0.97	D
Vest4		0.42
MutPred		0.25		Loss of MoRF binding (P = 0.0286)
MVP		0.39
ClinPred		0.39	T
GERP RS		3.5
Varity_R		0.26
gMVP		0.67
Mutation Taster		=95/5	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;