rs371033981

Variant names:

• chr12-119335181-C-A
• rs371033981
• NM_178499.5:c.5C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-119335181-C-A
• chr12-119335181-C-G
• chr12-119335181-C-T

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.5C>A​(p.Thr2Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000086 in 1,604,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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. T2I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000092 (0 hom.)
• Consequence: CCDC60 NM_178499.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.683
• Publications: 0 publications found

Genes affected

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

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=0.13142595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC60	NM_178499.5	c.5C>A	p.Thr2Asn	missense_variant	Exon 1 of 14	ENST00000327554.3	NP_848594.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC60	ENST00000327554.3	c.5C>A	p.Thr2Asn	missense_variant	Exon 1 of 14	1	NM_178499.5	ENSP00000333374.2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152132 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000241

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000330 AC: 8 AN: 242360 AF XY: 0.0000381

Gnomad AFR exome AF: 0.00

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: 0.0000717

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000916 AC: 133 AN: 1452544 Hom.: 0 Cov.: 30 AF XY: 0.0000927 AC XY: 67 AN XY: 722478

African (AFR) AF: 0.0000608 AC: 2 AN: 32918

American (AMR) AF: 0.00 AC: 0 AN: 42826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25910

East Asian (EAS) AF: 0.00 AC: 0 AN: 39126

South Asian (SAS) AF: 0.00 AC: 0 AN: 84296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.000115 AC: 128 AN: 1108354

Other (OTH) AF: 0.0000500 AC: 3 AN: 60032

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152132 Hom.: 0 Cov.: 30 AF XY: 0.0000538 AC XY: 4 AN XY: 74322

African (AFR) AF: 0.0000241 AC: 1 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.0000340

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000412 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Benign	0.00081	.;T;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.52	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	.;L;.
PhyloP100		0.68
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.021
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.033	.;B;.
Vest4		0.11
MVP		0.30
MPC		0.070
ClinPred		0.17	T
GERP RS		4.0
PromoterAI		0.021	Neutral
Varity_R		0.11
gMVP		0.20
Mutation Taster		=83/17	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: rs371033981; hg19: chr12-119772986;