17-44679001-C-G

Variant names:

• chr17-44679001-C-G
• NM_144609.3:c.530G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144609.3(CCDC43):​c.530G>C​(p.Arg177Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,662 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R177Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CCDC43 NM_144609.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.68

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]

LOC105371792 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23833963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC43	NM_144609.3	c.530G>C	p.Arg177Pro	missense_variant	Exon 5 of 5	ENST00000315286.13	NP_653210.2
CCDC43	NM_001099225.2	c.*6G>C		3_prime_UTR_variant	Exon 4 of 4		NP_001092695.1
LOC105371792	XR_007065769.1	n.38C>G		non_coding_transcript_exon_variant	Exon 1 of 4
LOC105371792	XR_934780.1	n.40C>G		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC43	ENST00000315286.13	c.530G>C	p.Arg177Pro	missense_variant	Exon 5 of 5	1	NM_144609.3	ENSP00000323782.7
CCDC43	ENST00000588210.1	c.539G>C	p.Arg180Pro	missense_variant	Exon 5 of 5	1		ENSP00000467630.1
CCDC43	ENST00000457422	c.*6G>C		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000400845.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461662 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727116

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.097	T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.14
Sift	Uncertain	0.010	D;.
Sift4G	Uncertain	0.035	D;D
Polyphen		0.99	D;.
Vest4		0.48
MutPred		0.38		Gain of loop (P = 0.0079);.;
MVP		0.30
MPC		0.77
ClinPred		0.91	D
GERP RS		4.2
Varity_R		0.63
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-42756369;