1-42545435-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001395517.1(CCDC30):c.746C>A(p.Ala249Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,426,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC30 NM_001395517.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.41

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
• BP6: Variant 1-42545435-C-A is Benign according to our data. Variant chr1-42545435-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2330722.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC30	NM_001395517.1	c.746C>A	p.Ala249Glu	missense_variant	9/21	ENST00000657597.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC30	ENST00000657597.2	c.746C>A	p.Ala249Glu	missense_variant	9/21		NM_001395517.1	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1426860 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 709412

Gnomad4 AFR exome AF: 0.00

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: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 01, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	14
Dann	Benign	0.36
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.48	T;T;.
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.024	T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Benign	0.28	T
REVEL	Benign	0.067
Polyphen		0.0	.;B;B
Vest4		0.12, 0.15
MutPred		0.37		.;Gain of solvent accessibility (P = 0.0145);Gain of solvent accessibility (P = 0.0145);
MVP		0.014
MPC		0.22
ClinPred		0.043	T
GERP RS		3.6
Varity_R		0.034
gMVP		0.030

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: 24

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-43011106;