1-42545564-A-T

Variant summary

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

The NM_001395517.1(CCDC30):c.875A>T(p.Glu292Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: CCDC30 NM_001395517.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.90

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=0.22257441).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC30	NM_001395517.1	c.875A>T	p.Glu292Val	missense_variant	9/21	ENST00000657597.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC30	ENST00000657597.2	c.875A>T	p.Glu292Val	missense_variant	9/21		NM_001395517.1	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 16, 2023

The c.410A>T (p.E137V) alteration is located in exon 4 (coding exon 3) of the CCDC30 gene. This alteration results from a A to T substitution at nucleotide position 410, causing the glutamic acid (E) at amino acid position 137 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
Cadd	Uncertain	25
Dann	Uncertain	0.99
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.62	T;T;.
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.61	T
MutationTaster	Benign	0.86	D;D;D;D;D
PrimateAI	Benign	0.35	T
REVEL	Benign	0.17
Polyphen		1.0	.;D;D
Vest4		0.39, 0.48
MutPred		0.076		.;Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.43
MPC		0.54
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.27
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1645111817; hg19: chr1-43011235;