chrX-49064547-C-G

Variant names:

• chrX-49064547-C-G
• NM_001163321.4:c.607C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001163321.4(CCDC120):​c.607C>G​(p.Arg203Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000094 in 1,064,037 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R203W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: CCDC120 NM_001163321.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC120	NM_001163321.4	c.607C>G	p.Arg203Gly	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.607C>G	p.Arg203Gly	missense_variant	Exon 6 of 11	2	NM_001163321.4	ENSP00000474071.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.40e-7 AC: 1 AN: 1064037 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 346301

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000121

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T;T;T;.;.
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.81	.;.;T;T;T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.57	D;D;D;D;D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.4	M;M;M;.;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.2	.;.;.;.;D
REVEL	Benign	0.17
Sift	Uncertain	0.0010	.;.;.;.;D
Sift4G	Benign	0.19	T;T;T;T;T
Polyphen		0.18	B;B;B;.;.
Vest4		0.59
MutPred		0.40		Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);.;.;
MVP		0.27
ClinPred		0.98	D
GERP RS		3.5
Varity_R		0.60
gMVP		0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-48922078;