17-44689725-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144609.3(CCDC43):​c.29T>C​(p.Ile10Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC43 NM_144609.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: 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=0.049318165).

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>C	p.Ile10Thr	missense	Exon 1 of 5	NP_653210.2	Q96MW1-1
	CCDC43	NM_001099225.2		c.29T>C	p.Ile10Thr	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>C	p.Ile10Thr	missense	Exon 1 of 5	ENSP00000323782.7	Q96MW1-1
	CCDC43	ENST00000588210.1	TSL:1	c.29T>C	p.Ile10Thr	missense	Exon 1 of 5	ENSP00000467630.1	Q86WV7
	CCDC43	ENST00000457422.6	TSL:1	c.29T>C	p.Ile10Thr	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: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.8
DANN	Benign	0.39
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0053	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		1.8
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.031
Sift	Benign	0.25	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.34		Gain of glycosylation at I10 (P = 0.0031)
MVP		0.055
MPC		0.25
ClinPred		0.11	T
GERP RS		2.3
PromoterAI		0.053	Neutral
Varity_R		0.036
gMVP		0.12

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;