17-44689698-C-T

Variant names:

• chr17-44689698-C-T
• rs755428500
• NM_144609.3:c.56G>A

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.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. 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: 6.9e-7 (0 hom.)
• Consequence: CCDC43 NM_144609.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0630
• 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=0.07380065).

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.56G>A	p.Gly19Asp	missense	Exon 1 of 5	NP_653210.2	Q96MW1-1
	CCDC43	NM_001099225.2		c.56G>A	p.Gly19Asp	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.56G>A	p.Gly19Asp	missense	Exon 1 of 5	ENSP00000323782.7	Q96MW1-1
	CCDC43	ENST00000588210.1	TSL:1	c.56G>A	p.Gly19Asp	missense	Exon 1 of 5	ENSP00000467630.1	Q86WV7
	CCDC43	ENST00000457422.6	TSL:1	c.56G>A	p.Gly19Asp	missense	Exon 1 of 4	ENSP00000400845.1	Q96MW1-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453038 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722260

African (AFR) AF: 0.00 AC: 0 AN: 33252

American (AMR) AF: 0.00 AC: 0 AN: 43014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25966

East Asian (EAS) AF: 0.00 AC: 0 AN: 39312

South Asian (SAS) AF: 0.00 AC: 0 AN: 85120

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 52134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108410

Other (OTH) AF: 0.00 AC: 0 AN: 60072

GnomAD4 genome Cov.: 32

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	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.80
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.035	N
PhyloP100		0.063
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.73	N
REVEL	Benign	0.025
Sift	Benign	0.084	T
Sift4G	Benign	0.31	T
Polyphen		0.039	B
Vest4		0.33
MutPred		0.24		Gain of helix (P = 0.0893)
MVP		0.061
MPC		0.52
ClinPred		0.096	T
GERP RS		-3.1
PromoterAI		0.00010	Neutral
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

Other links and lift over

dbSNP: rs755428500; hg19: chr17-42767066;