Variant 17-44678945-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_144609.3(CCDC43):c.586A>C(p.Lys196Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

CCDC43
NM_144609.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.08

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:

MEIOC (HGNC:):

MEIOC links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39841807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC43	NM_144609.3 linkuse as main transcript	c.586A>C	p.Lys196Gln	missense_variant	5/5	ENST00000315286.13	NP_653210.2	Q96MW1-1
CCDC43	NM_001099225.2 linkuse as main transcript	c.*62A>C		3_prime_UTR_variant	4/4		NP_001092695.1	Q96MW1-2
LOC105371792	XR_007065769.1 linkuse as main transcript	n.-19T>G		upstream_gene_variant
LOC105371792	XR_934780.1 linkuse as main transcript	n.-17T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC43	ENST00000315286.13 linkuse as main transcript	c.586A>C	p.Lys196Gln	missense_variant	5/5	1	NM_144609.3	ENSP00000323782.7	Q96MW1-1
CCDC43	ENST00000588210.1 linkuse as main transcript	c.595A>C	p.Lys199Gln	missense_variant	5/5	1		ENSP00000467630.1	Q86WV7
CCDC43	ENST00000457422.6 linkuse as main transcript	c.*62A>C		3_prime_UTR_variant	4/4	1		ENSP00000400845.1	Q96MW1-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461698

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727130

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:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Dec 16, 2023

The c.586A>C (p.K196Q) alteration is located in exon 5 (coding exon 5) of the CCDC43 gene. This alteration results from a A to C substitution at nucleotide position 586, causing the lysine (K) at amino acid position 196 to be replaced by a glutamine (Q). 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

0.34

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

T;T

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.40

T;T

MetaSVM

Uncertain

-0.018

MutationAssessor

Pathogenic

3.1

M;.

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.3

D;.

REVEL

Uncertain

0.31

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.026

D;D

Polyphen

0.98

D;.

Vest4

0.46

MutPred

0.14

Loss of methylation at K196 (P = 0.0128);.;

MVP

0.42

MPC

0.76

ClinPred

0.98

GERP RS

6.2

Varity_R

0.47

gMVP

0.20

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over