NM_144609.3:c.29T>G

Variant names:

• chr17-44689725-A-C
• rs1005688570
• NM_144609.3:c.29T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144609.3(CCDC43):​c.29T>G​(p.Ile10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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. I10T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC43 NM_144609.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• Publications: 0 publications found

Genes affected

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

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]

ENSG00000279879 (HGNC:):

ACMG classification

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=0.08573112).

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.29T>G	p.Ile10Arg	missense	Exon 1 of 5	NP_653210.2	Q96MW1-1
	CCDC43	NM_001099225.2		c.29T>G	p.Ile10Arg	missense	Exon 1 of 4	NP_001092695.1	Q96MW1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC43	ENST00000315286.13	TSL:1 MANE Select	c.29T>G	p.Ile10Arg	missense	Exon 1 of 5	ENSP00000323782.7	Q96MW1-1
	CCDC43	ENST00000588210.1	TSL:1	c.29T>G	p.Ile10Arg	missense	Exon 1 of 5	ENSP00000467630.1	Q86WV7
	CCDC43	ENST00000457422.6	TSL:1	c.29T>G	p.Ile10Arg	missense	Exon 1 of 4	ENSP00000400845.1	Q96MW1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.82
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.24
Sift	Benign	0.032	D
Sift4G	Uncertain	0.029	D
Polyphen		0.0	B
Vest4		0.29
MutPred		0.35		Gain of disorder (P = 0.0216)
MVP		0.10
MPC		0.35
ClinPred		0.089	T
GERP RS		2.3
PromoterAI		0.051	Neutral
Varity_R		0.067
gMVP		0.13

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

Other links and lift over

dbSNP: rs1005688570; hg19: chr17-42767093;