chr12-119428721-C-G

Variant names:

• chr12-119428721-C-G
• NM_178499.5:c.129C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178499.5(CCDC60):​c.129C>G​(p.Asp43Glu) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC60 NM_178499.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0740
• Publications: 0 publications found

Genes affected

CCDC60 (HGNC:28610): (coiled-coil domain containing 60)

ENSG00000248636 (HGNC:58183):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0928891).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC60	NM_178499.5	c.129C>G	p.Asp43Glu	missense_variant	Exon 2 of 14	ENST00000327554.3	NP_848594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC60	ENST00000327554.3	c.129C>G	p.Asp43Glu	missense_variant	Exon 2 of 14	1	NM_178499.5	ENSP00000333374.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.129C>G (p.D43E) alteration is located in exon 2 (coding exon 2) of the CCDC60 gene. This alteration results from a C to G substitution at nucleotide position 129, causing the aspartic acid (D) at amino acid position 43 to be replaced by a glutamic acid (E). 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	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Benign	0.0044	.;T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.49	T;T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.093	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.84	.;L;.
PhyloP100		0.074
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.9	D;N;D
REVEL	Benign	0.086
Sift	Uncertain	0.011	D;T;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.0020	.;B;.
Vest4		0.095
MutPred		0.49		Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);
MVP		0.33
MPC		0.059
ClinPred		0.073	T
GERP RS		1.7
Varity_R		0.060
gMVP		0.044
Mutation Taster		=95/5	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

hg19: chr12-119866526;