Genetic Variant NM_001395517.1:c.542G>C (chr1-42536561-G-C) – 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.542G>C(p.Gly181Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.0000014 ( 0 hom. )

Consequence

CCDC30
NM_001395517.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.394

Publications

0 publications found

Variant links:

Genes affected

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

CCDC30 links:

Genome browser will be placed here

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=0.044612586).

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.542G>C	p.Gly181Ala	missense	Exon 7 of 21	NP_001382446.1	A0A590UK19
CCDC30	NM_001080850.4		c.77G>C	p.Gly26Ala	missense	Exon 3 of 17	NP_001074319.1	Q5VVM6-1
CCDC30	NM_001395379.1		c.542G>C	p.Gly181Ala	missense	Exon 7 of 18	NP_001382308.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC30	ENST00000657597.2	MANE Select	c.542G>C	p.Gly181Ala	missense	Exon 7 of 21	ENSP00000499662.2	A0A590UK19
CCDC30	ENST00000477155.6	TSL:1	n.*620G>C		non_coding_transcript_exon	Exon 9 of 23	ENSP00000421479.3	D6RFH8
CCDC30	ENST00000477155.6	TSL:1	n.*620G>C		3_prime_UTR	Exon 9 of 23	ENSP00000421479.3	D6RFH8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251336

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461240

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726928

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111578

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.91

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.0012

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.40

M_CAP

Benign

0.0088

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PhyloP100

0.39

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.3

REVEL

Benign

0.036

Sift

Benign

0.39

Sift4G

Benign

0.76

Polyphen

0.0030

Vest4

0.089

MutPred

0.15

Loss of relative solvent accessibility (P = 0.0071)

MVP

0.014

MPC

0.21

ClinPred

0.026

GERP RS

-1.1

PromoterAI

0.0054

Neutral

(source)

Varity_R

0.033

gMVP

0.053

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over