chrX-49063927-C-T

Variant names:

• chrX-49063927-C-T
• rs782132519
• NM_001163321.4:c.355C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_001163321.4(CCDC120):​c.355C>T​(p.Arg119Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,207,402 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000031 (0 hom. 15 hem.)
• Consequence: CCDC120 NM_001163321.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.662
• Publications: 1 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 -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762
• BS2: High Hemizygotes in GnomAdExome4 at 15 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.355C>T	p.Arg119Trp	missense	Exon 5 of 11	NP_001156793.2	Q96HB5-4
	CCDC120	NM_001163322.2		c.214C>T	p.Arg72Trp	missense	Exon 5 of 11	NP_001156794.1	Q96HB5-5
	CCDC120	NM_001271835.1		c.250C>T	p.Arg84Trp	missense	Exon 5 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.355C>T	p.Arg119Trp	missense	Exon 5 of 11	ENSP00000474071.1	Q96HB5-4
	CCDC120	ENST00000606812.5	TSL:1	c.250C>T	p.Arg84Trp	missense	Exon 5 of 10	ENSP00000475676.1	Q96HB5-1
	CCDC120	ENST00000603906.2	TSL:2	c.214C>T	p.Arg72Trp	missense	Exon 5 of 11	ENSP00000474713.2	Q96HB5-5

Frequencies

GnomAD3 genomes AF: 0.0000270 AC: 3 AN: 111176 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000327

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000956

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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000172 AC: 3 AN: 174498 AF XY: 0.0000163

Gnomad AFR exome AF: 0.0000808

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: 0.0000130

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000310 AC: 34 AN: 1096226 Hom.: 0 Cov.: 31 AF XY: 0.0000415 AC XY: 15 AN XY: 361810

African (AFR) AF: 0.000190 AC: 5 AN: 26355

American (AMR) AF: 0.00 AC: 0 AN: 35038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19319

East Asian (EAS) AF: 0.00 AC: 0 AN: 30085

South Asian (SAS) AF: 0.00 AC: 0 AN: 53797

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40329

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.0000309 AC: 26 AN: 841203

Other (OTH) AF: 0.0000653 AC: 3 AN: 45968

GnomAD4 genome AF: 0.0000270 AC: 3 AN: 111176 Hom.: 0 Cov.: 23 AF XY: 0.0000300 AC XY: 1 AN XY: 33362

African (AFR) AF: 0.0000327 AC: 1 AN: 30541

American (AMR) AF: 0.0000956 AC: 1 AN: 10461

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2639

East Asian (EAS) AF: 0.00 AC: 0 AN: 3528

South Asian (SAS) AF: 0.00 AC: 0 AN: 2642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52914

Other (OTH) AF: 0.00 AC: 0 AN: 1472

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.00000825 AC: 1

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	0.22
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.51	D
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.66
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-7.1	D
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.45		Gain of catalytic residue at P87 (P = 0.0428)
MVP		0.36
ClinPred		0.97	D
GERP RS		3.7
Varity_R		0.66
gMVP		0.71
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: rs782132519; hg19: chrX-48921458; COSMIC: COSV64515487; COSMIC: COSV64515487;