Genetic Variant NM_144609.3:c.47A>C (chr17-44689707-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144609.3(CCDC43):c.47A>C(p.Asp16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,448,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 0.0000021 ( 0 hom. )

Consequence

CCDC43
NM_144609.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0820

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07216489).

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.47A>C	p.Asp16Ala	missense	Exon 1 of 5	NP_653210.2	Q96MW1-1
	CCDC43	NM_001099225.2		c.47A>C	p.Asp16Ala	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.47A>C	p.Asp16Ala	missense	Exon 1 of 5	ENSP00000323782.7	Q96MW1-1
CCDC43	ENST00000588210.1	TSL:1	c.47A>C	p.Asp16Ala	missense	Exon 1 of 5	ENSP00000467630.1	Q86WV7
CCDC43	ENST00000457422.6	TSL:1	c.47A>C	p.Asp16Ala	missense	Exon 1 of 4	ENSP00000400845.1	Q96MW1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000453

AC:

AN:

220692

AF XY:

0.00000833

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1448790

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

719776

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33178

American (AMR)

AF:

0.00

AC:

AN:

42210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25870

East Asian (EAS)

AF:

0.00

AC:

AN:

39066

South Asian (SAS)

AF:

0.00

AC:

AN:

84518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51842

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1106430

Other (OTH)

AF:

0.00

AC:

AN:

59930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000831

AC:

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

0.061

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.013

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.30

M_CAP

Benign

0.0059

MetaRNN

Benign

0.072

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.082

PrimateAI

Benign

0.42

PROVEAN

Benign

0.030

REVEL

Benign

0.012

Sift

Benign

0.046

Sift4G

Benign

0.14

Polyphen

0.0080

Vest4

0.26

MutPred

0.24

Loss of loop (P = 0.0235)

MVP

0.17

MPC

0.30

ClinPred

0.078

GERP RS

0.64

PromoterAI

-0.14

Neutral

(source)

Varity_R

0.055

gMVP

0.16

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over