Genetic Variant CCDC30:p.Asp333Asn (chr1-42556262-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001395517.1(CCDC30):c.997G>A(p.Asp333Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. D333Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCDC30
NM_001395517.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.412

Publications

1 publications found

Variant links:

Genes affected

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

CCDC30 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057230264).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395517.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC30	NM_001395517.1	MANE Select	c.997G>A	p.Asp333Asn	missense	Exon 10 of 21	NP_001382446.1	A0A590UK19
CCDC30	NM_001080850.4		c.532G>A	p.Asp178Asn	missense	Exon 6 of 17	NP_001074319.1	Q5VVM6-1
CCDC30	NM_001355224.2		c.-513G>A		5_prime_UTR	Exon 11 of 23	NP_001342153.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC30	ENST00000657597.2	MANE Select	c.997G>A	p.Asp333Asn	missense	Exon 10 of 21	ENSP00000499662.2	A0A590UK19
CCDC30	ENST00000514642.1	TSL:1	c.28-10034G>A		intron	N/A	ENSP00000499505.1	A0A590UJL6
CCDC30	ENST00000477155.6	TSL:1	n.*937G>A		non_coding_transcript_exon	Exon 11 of 23	ENSP00000421479.3	D6RFH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727190

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111958

Other (OTH)

AF:

0.00

AC:

AN:

60386

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0054

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.51

M_CAP

Benign

0.014

MetaRNN

Benign

0.057

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

0.41

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.91

REVEL

Benign

0.022

Sift

Benign

0.31

Sift4G

Benign

0.47

Polyphen

0.19

Vest4

0.087

MutPred

0.12

Loss of stability (P = 0.0578)

MVP

0.12

MPC

0.23

ClinPred

0.17

GERP RS

3.1

Varity_R

0.037

gMVP

0.069

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over