X-49064509-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/19 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC120	NM_001163321.4	c.569G>C	p.Arg190Thr	missense_variant	Exon 6 of 11	ENST00000603986.6	NP_001156793.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC120	ENST00000603986.6	c.569G>C	p.Arg190Thr	missense_variant	Exon 6 of 11	2	NM_001163321.4	ENSP00000474071.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.0000153 AC: 2 AN: 131003 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 40985

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 SAS 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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000642

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 11, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.464G>C (p.R155T) alteration is located in exon 6 (coding exon 4) of the CCDC120 gene. This alteration results from a G to C substitution at nucleotide position 464, causing the arginine (R) at amino acid position 155 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T;.;.
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	.;.;T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.27	T;T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.1	L;L;L;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.4	.;.;.;.;D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	.;.;.;.;D
Sift4G	Benign	0.075	T;T;T;T;T
Polyphen		0.97	D;D;D;.;.
Vest4		0.42
MutPred		0.25		Loss of MoRF binding (P = 0.0286);Loss of MoRF binding (P = 0.0286);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1557080491; hg19: chrX-48922040;