rs1366838657

Variant names:

• chrX-49065486-C-T
• rs1366838657
• NM_001163321.4:c.820C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001163321.4(CCDC120):​c.820C>T​(p.Arg274Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000551 in 1,088,679 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts 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. R274H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000055 (0 hom. 2 hem.)
• Consequence: CCDC120 NM_001163321.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.97
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1876418).
• BS2: High Hemizygotes in GnomAdExome4 at 2 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC120	NM_001163321.4	MANE Select	c.820C>T	p.Arg274Cys	missense	Exon 8 of 11	NP_001156793.2	Q96HB5-4
	CCDC120	NM_001163322.2		c.679C>T	p.Arg227Cys	missense	Exon 8 of 11	NP_001156794.1	Q96HB5-5
	CCDC120	NM_001271835.1		c.715C>T	p.Arg239Cys	missense	Exon 8 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.820C>T	p.Arg274Cys	missense	Exon 8 of 11	ENSP00000474071.1	Q96HB5-4
	CCDC120	ENST00000606812.5	TSL:1	c.715C>T	p.Arg239Cys	missense	Exon 8 of 10	ENSP00000475676.1	Q96HB5-1
	CCDC120	ENST00000603906.2	TSL:2	c.679C>T	p.Arg227Cys	missense	Exon 8 of 11	ENSP00000474713.2	Q96HB5-5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000551 AC: 6 AN: 1088679 Hom.: 0 Cov.: 32 AF XY: 0.00000561 AC XY: 2 AN XY: 356579

African (AFR) AF: 0.00 AC: 0 AN: 25976

American (AMR) AF: 0.00 AC: 0 AN: 33020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18754

East Asian (EAS) AF: 0.00 AC: 0 AN: 30104

South Asian (SAS) AF: 0.00 AC: 0 AN: 52322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4062

European-Non Finnish (NFE) AF: 0.00000715 AC: 6 AN: 838613

Other (OTH) AF: 0.00 AC: 0 AN: 45662

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.19
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.28	T
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.083	T
Polyphen		1.0	D
Vest4		0.36
MutPred		0.20		Loss of phosphorylation at S241 (P = 0.0554)
MVP		0.19
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.40
gMVP		0.46
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1366838657; hg19: chrX-48923017;