17-44678945-T-G

Variant names:

• chr17-44678945-T-G
• rs914620971
• NM_144609.3:c.586A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144609.3(CCDC43):​c.586A>C​(p.Lys196Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K196E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: CCDC43 NM_144609.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.08
• 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]

LOC105371792 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39841807).

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.586A>C	p.Lys196Gln	missense	Exon 5 of 5	NP_653210.2	Q96MW1-1
	CCDC43	NM_001099225.2		c.*62A>C		3_prime_UTR	Exon 4 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.586A>C	p.Lys196Gln	missense	Exon 5 of 5	ENSP00000323782.7	Q96MW1-1
	CCDC43	ENST00000588210.1	TSL:1	c.595A>C	p.Lys199Gln	missense	Exon 5 of 5	ENSP00000467630.1	Q86WV7
	CCDC43	ENST00000457422.6	TSL:1	c.*62A>C		3_prime_UTR	Exon 4 of 4	ENSP00000400845.1	Q96MW1-2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152122 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461698 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727130

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111866

Other (OTH) AF: 0.0000166 AC: 1 AN: 60372

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152122 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.34
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.40	T
MetaSVM	Uncertain	-0.018	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		7.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.026	D
Polyphen		0.98	D
Vest4		0.46
MutPred		0.14		Loss of methylation at K196 (P = 0.0128)
MVP		0.42
MPC		0.76
ClinPred		0.98	D
GERP RS		6.2
Varity_R		0.47
gMVP		0.20
Mutation Taster		=53/47	polymorphism

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: rs914620971; hg19: chr17-42756313;