Genetic Variant CCDC43:p.Ala11Thr (chr17-44689723-C-T) – 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_144609.3(CCDC43):c.31G>A(p.Ala11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A11S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CCDC43
NM_144609.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.243

Publications

0 publications found

Variant links:

Genes affected

CCDC43 (HGNC:26472): (coiled-coil domain containing 43) Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

CCDC43 links:

MEIOC (HGNC:26670): (meiosis specific with coiled-coil domain) Predicted to be involved in several processes, including gamete generation; germline cell cycle switching, mitotic to meiotic cell cycle; and mRNA stabilization. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MEIOC links:

ENSG00000279879 (HGNC:):

ENSG00000279879 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=0.066649824).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144609.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC43	NM_144609.3	MANE Select	c.31G>A	p.Ala11Thr	missense	Exon 1 of 5	NP_653210.2	Q96MW1-1
	CCDC43	NM_001099225.2		c.31G>A	p.Ala11Thr	missense	Exon 1 of 4	NP_001092695.1	Q96MW1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC43	ENST00000315286.13	TSL:1 MANE Select	c.31G>A	p.Ala11Thr	missense	Exon 1 of 5	ENSP00000323782.7	Q96MW1-1
CCDC43	ENST00000588210.1	TSL:1	c.31G>A	p.Ala11Thr	missense	Exon 1 of 5	ENSP00000467630.1	Q86WV7
CCDC43	ENST00000457422.6	TSL:1	c.31G>A	p.Ala11Thr	missense	Exon 1 of 4	ENSP00000400845.1	Q96MW1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1432164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710032

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32714

American (AMR)

AF:

0.00

AC:

AN:

39574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25606

East Asian (EAS)

AF:

0.00

AC:

AN:

37960

South Asian (SAS)

AF:

0.00

AC:

AN:

82710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49832

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

9.10e-7

AC:

AN:

1098666

Other (OTH)

AF:

0.00

AC:

AN:

59416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.0

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.030

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.34

M_CAP

Benign

0.0024

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

0.24

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.83

REVEL

Benign

0.059

Sift

Benign

0.040

Sift4G

Benign

0.069

Polyphen

0.0

Vest4

0.14

MutPred

0.27

Gain of glycosylation at A11 (P = 0.0141)

MVP

0.088

MPC

0.19

ClinPred

0.088

GERP RS

-2.0

PromoterAI

0.017

Neutral

(source)

Varity_R

0.063

gMVP

0.20

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