17-44678927-C-T

Variant names:

• chr17-44678927-C-T
• rs760437694
• NM_144609.3:c.604G>A

Variant summary

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

The NM_144609.3(CCDC43):​c.604G>A​(p.Asp202Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,642 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. D202H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC43 NM_144609.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21
• 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=0.3047579).

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.604G>A	p.Asp202Asn	missense	Exon 5 of 5	NP_653210.2	Q96MW1-1
	CCDC43	NM_001099225.2		c.*80G>A		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.604G>A	p.Asp202Asn	missense	Exon 5 of 5	ENSP00000323782.7	Q96MW1-1
	CCDC43	ENST00000588210.1	TSL:1	c.613G>A	p.Asp205Asn	missense	Exon 5 of 5	ENSP00000467630.1	Q86WV7
	CCDC43	ENST00000457422.6	TSL:1	c.*80G>A		3_prime_UTR	Exon 4 of 4	ENSP00000400845.1	Q96MW1-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461642 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727100

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111830

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.30	T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.2
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.17
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.017	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.18		Loss of stability (P = 0.0517)
MVP		0.47
MPC		0.41
ClinPred		0.91	D
GERP RS		6.2
Varity_R		0.084
gMVP		0.066

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: rs760437694; hg19: chr17-42756295;