X-49064571-C-T

Variant names:

• chrX-49064571-C-T
• NM_001163321.4:c.631C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001163321.4(CCDC120):​c.631C>T​(p.Leu211Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: CCDC120 NM_001163321.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.285

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08602953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC120	NM_001163321.4	c.631C>T	p.Leu211Phe	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.631C>T	p.Leu211Phe	missense_variant	Exon 6 of 11	2	NM_001163321.4	ENSP00000474071.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.526C>T (p.L176F) alteration is located in exon 6 (coding exon 4) of the CCDC120 gene. This alteration results from a C to T substitution at nucleotide position 526, causing the leucine (L) at amino acid position 176 to be replaced by a phenylalanine (F). 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	0.098
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.047	T;T;T;.;.
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.72	.;.;T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.086	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.64	.;.;.;.;N
REVEL	Benign	0.016
Sift	Uncertain	0.0080	.;.;.;.;D
Sift4G	Benign	0.079	T;T;T;T;T
Polyphen		0.23	B;B;B;.;.
Vest4		0.12
MutPred		0.27		Loss of disorder (P = 0.0599);Loss of disorder (P = 0.0599);Loss of disorder (P = 0.0599);.;.;
MVP		0.068
ClinPred		0.089	T
GERP RS		-1.3
Varity_R		0.17
gMVP		0.38

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-48922102;