12-119428756-G-T

Variant names:

• chr12-119428756-G-T
• rs764208425
• NM_178499.5:c.164G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_178499.5(CCDC60):​c.164G>T​(p.Arg55Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,438,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R55Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC60 NM_178499.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC60	NM_178499.5	c.164G>T	p.Arg55Leu	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.164G>T	p.Arg55Leu	missense_variant	Exon 2 of 14	1	NM_178499.5	ENSP00000333374.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1438908 Hom.: 0 Cov.: 28 AF XY: 0.00000280 AC XY: 2 AN XY: 714764

African (AFR) AF: 0.00 AC: 0 AN: 33176

American (AMR) AF: 0.00 AC: 0 AN: 42916

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25704

East Asian (EAS) AF: 0.00 AC: 0 AN: 39502

South Asian (SAS) AF: 0.00 AC: 0 AN: 83444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52510

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1096252

Other (OTH) AF: 0.00 AC: 0 AN: 59662

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	.;T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	1.2	.;L;.
PhyloP100		2.6
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-7.0	D;D;D
REVEL	Benign	0.23
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;T;D
Polyphen		1.0	.;D;.
Vest4		0.55
MutPred		0.66		Gain of catalytic residue at R57 (P = 0.0067);Gain of catalytic residue at R57 (P = 0.0067);Gain of catalytic residue at R57 (P = 0.0067);
MVP		0.68
MPC		0.41
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.24
gMVP		0.17
Mutation Taster		=71/29	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

dbSNP: rs764208425; hg19: chr12-119866561;