1-42581396-A-G

Variant summary

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

The NM_001395517.1(CCDC30):c.1567A>G(p.Lys523Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: CCDC30 NM_001395517.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.850

Genes affected

CCDC30 (HGNC:26103): (coiled-coil domain containing 30)

LOC124904162 (HGNC:):

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=0.12163323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC30	NM_001395517.1	c.1567A>G	p.Lys523Glu	missense_variant	13/21	ENST00000657597.2
LOC124904162	XR_007066034.1	n.77-10236T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC30	ENST00000657597.2	c.1567A>G	p.Lys523Glu	missense_variant	13/21		NM_001395517.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000161 AC: 4 AN: 249094 Hom.: 0 AF XY: 0.0000149 AC XY: 2 AN XY: 134584

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1459694 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726098

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.0000546

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.1102A>G (p.K368E) alteration is located in exon 8 (coding exon 7) of the CCDC30 gene. This alteration results from a A to G substitution at nucleotide position 1102, causing the lysine (K) at amino acid position 368 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	0.10
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.44
Cadd	Benign	19
Dann	Uncertain	0.99
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.61	T;T;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.28	T
REVEL	Benign	0.13
Polyphen		0.89	.;P;P
Vest4		0.30, 0.29
MutPred		0.42		.;Loss of ubiquitination at K368 (P = 0.0077);Loss of ubiquitination at K368 (P = 0.0077);
MVP		0.36
MPC		0.82
ClinPred		0.71	D
GERP RS		3.1
Varity_R		0.13
gMVP		0.020

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

LitVar

Other links and lift over

dbSNP: rs770018297; hg19: chr1-43047067;