1-42556356-T-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.1091T>G(p.Leu364Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: CCDC30 NM_001395517.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41

Genes affected

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

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=0.24005875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC30	NM_001395517.1	c.1091T>G	p.Leu364Arg	missense_variant	10/21	ENST00000657597.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC30	ENST00000657597.2	c.1091T>G	p.Leu364Arg	missense_variant	10/21		NM_001395517.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461816 Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15 AN XY: 727204

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Oct 03, 2022

The c.626T>G (p.L209R) alteration is located in exon 5 (coding exon 4) of the CCDC30 gene. This alteration results from a T to G substitution at nucleotide position 626, causing the leucine (L) at amino acid position 209 to be replaced by an arginine (R). 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	0.13
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
Cadd	Benign	20
Dann	Uncertain	1.0
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.54	T;T;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.81	T
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Benign	0.35	T
REVEL	Benign	0.24
Polyphen		0.99	.;D;D
Vest4		0.43, 0.83
MutPred		0.30		.;Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);
MVP		0.65
MPC		0.86
ClinPred		0.91	D
GERP RS		5.1
Varity_R		0.43
gMVP		0.13

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: rs895620246; hg19: chr1-43022027;