Variant 17-44689698-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144609.3(CCDC43):c.56G>A(p.Gly19Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 6.9e-7 ( 0 hom. )

Consequence

CCDC43
NM_144609.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0630

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:

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ACMG classification

Classification made for transcript

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=0.07380065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC43	NM_144609.3 linkuse as main transcript	c.56G>A	p.Gly19Asp	missense_variant	1/5	ENST00000315286.13	NP_653210.2
CCDC43	NM_001099225.2 linkuse as main transcript	c.56G>A	p.Gly19Asp	missense_variant	1/4		NP_001092695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC43	ENST00000315286.13 linkuse as main transcript	c.56G>A	p.Gly19Asp	missense_variant	1/5	1	NM_144609.3	ENSP00000323782	P2	Q96MW1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453038

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722260

show subpopulations

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:

0.0000192

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2023

The c.56G>A (p.G19D) alteration is located in exon 1 (coding exon 1) of the CCDC43 gene. This alteration results from a G to A substitution at nucleotide position 56, causing the glycine (G) at amino acid position 19 to be replaced by an aspartic acid (D). 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

0.10

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.015

.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.52

T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.074

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.035

N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

0.73

N;N;.

REVEL

Benign

0.025

Sift

Benign

0.084

T;T;.

Sift4G

Benign

0.31

T;T;T

Polyphen

0.039

B;B;.

Vest4

0.33

MutPred

0.24

Gain of helix (P = 0.0893);Gain of helix (P = 0.0893);Gain of helix (P = 0.0893);

MVP

0.061

MPC

0.52

ClinPred

0.096

GERP RS

-3.1

Varity_R

0.050

gMVP

0.19

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over