chr12-119488760-G-A

Variant names:

• chr12-119488760-G-A
• rs144745942
• NM_178499.5:c.451G>A

Variant summary

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

The NM_178499.5(CCDC60):​c.451G>A​(p.Glu151Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000128 in 1,613,554 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: CCDC60 NM_178499.5 missense, splice_region
• Scores: Splicing: ADA: 0.9392
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.32
• Publications: 4 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC60	NM_178499.5	c.451G>A	p.Glu151Lys	missense_variant, splice_region_variant	Exon 5 of 14	ENST00000327554.3	NP_848594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC60	ENST00000327554.3	c.451G>A	p.Glu151Lys	missense_variant, splice_region_variant	Exon 5 of 14	1	NM_178499.5	ENSP00000333374.2

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000517 AC: 13 AN: 251352 AF XY: 0.0000368

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000129 AC: 189 AN: 1461460 Hom.: 0 Cov.: 30 AF XY: 0.000127 AC XY: 92 AN XY: 727036

African (AFR) AF: 0.0000896 AC: 3 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000157 AC: 174 AN: 1111616

Other (OTH) AF: 0.000182 AC: 11 AN: 60376

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152094 Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7 AN XY: 74296

African (AFR) AF: 0.0000724 AC: 3 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68012

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000135 Hom.: 0

Bravo AF: 0.000117

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000577 AC: 7

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.451G>A (p.E151K) alteration is located in exon 5 (coding exon 5) of the CCDC60 gene. This alteration results from a G to A substitution at nucleotide position 451, causing the glutamic acid (E) at amino acid position 151 to be replaced by a lysine (K). 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	0.33
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.3
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.079
Sift	Benign	0.16	T
Sift4G	Uncertain	0.016	D
Polyphen		0.99	D
Vest4		0.71
MVP		0.29
MPC		0.37
ClinPred		0.43	T
GERP RS		5.1
Varity_R		0.17
gMVP		0.50
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.94
dbscSNV1_RF	Pathogenic	0.86
SpliceAI score (max)		0.030		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: rs144745942; hg19: chr12-119926565; COSMIC: COSV59539857;