X-49064452-C-T

Variant names:

• chrX-49064452-C-T
• rs782203688
• NM_001163321.4:c.512C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001163321.4(CCDC120):​c.512C>T​(p.Pro171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000151 in 1,179,055 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 55 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., 7 hem., cov: 24)
  • Exomes 𝑓: 0.00016 (0 hom. 48 hem.)
• Consequence: CCDC120 NM_001163321.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008667171).
• BS2: High Hemizygotes in GnomAd4 at 7 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.512C>T	p.Pro171Leu	missense	Exon 6 of 11	NP_001156793.2	Q96HB5-4
	CCDC120	NM_001163322.2		c.371C>T	p.Pro124Leu	missense	Exon 6 of 11	NP_001156794.1	Q96HB5-5
	CCDC120	NM_001271835.1		c.407C>T	p.Pro136Leu	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.512C>T	p.Pro171Leu	missense	Exon 6 of 11	ENSP00000474071.1	Q96HB5-4
	CCDC120	ENST00000606812.5	TSL:1	c.407C>T	p.Pro136Leu	missense	Exon 6 of 10	ENSP00000475676.1	Q96HB5-1
	CCDC120	ENST00000603906.2	TSL:2	c.371C>T	p.Pro124Leu	missense	Exon 6 of 11	ENSP00000474713.2	Q96HB5-5

Frequencies

GnomAD3 genomes AF: 0.000107 AC: 12 AN: 112504 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000641

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000151

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000155 AC: 19 AN: 122499 AF XY: 0.000101

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00132

Gnomad NFE exome AF: 0.0000823

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000156 AC: 166 AN: 1066551 Hom.: 0 Cov.: 32 AF XY: 0.000138 AC XY: 48 AN XY: 347423

African (AFR) AF: 0.00 AC: 0 AN: 25476

American (AMR) AF: 0.00 AC: 0 AN: 30441

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18840

East Asian (EAS) AF: 0.00 AC: 0 AN: 28095

South Asian (SAS) AF: 0.00 AC: 0 AN: 50721

European-Finnish (FIN) AF: 0.000744 AC: 28 AN: 37613

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3084

European-Non Finnish (NFE) AF: 0.000153 AC: 127 AN: 827473

Other (OTH) AF: 0.000245 AC: 11 AN: 44808

GnomAD4 genome AF: 0.000107 AC: 12 AN: 112504 Hom.: 0 Cov.: 24 AF XY: 0.000202 AC XY: 7 AN XY: 34682

African (AFR) AF: 0.00 AC: 0 AN: 31056

American (AMR) AF: 0.00 AC: 0 AN: 10805

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2655

East Asian (EAS) AF: 0.00 AC: 0 AN: 3515

South Asian (SAS) AF: 0.00 AC: 0 AN: 2786

European-Finnish (FIN) AF: 0.000641 AC: 4 AN: 6238

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

European-Non Finnish (NFE) AF: 0.000151 AC: 8 AN: 53022

Other (OTH) AF: 0.00 AC: 0 AN: 1519

Alfa AF: 0.000285 Hom.: 2

Bravo AF: 0.0000604

ExAC AF: 0.0000442 AC: 5

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	0.25
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.87	D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.0087	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.4
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Benign	0.16
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.026	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.27		Gain of helix (P = 0.005)
MVP		0.27
ClinPred		0.49	T
GERP RS		4.8
Varity_R		0.73
gMVP		0.66
Mutation Taster		=100/0	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: rs782203688; hg19: chrX-48921983;