17-44902549-A-G

Variant names:

• chr17-44902549-A-G
• NM_213607.3:c.461A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_213607.3(CCDC103):​c.461A>G​(p.His154Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. H154P) has been classified as Pathogenic.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: CCDC103 NM_213607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28

Genes affected

CCDC103 (HGNC:32700): (coiled-coil domain containing 103) Enables protein homodimerization activity. Involved in axonemal dynein complex assembly; cilium movement; and determination of left/right symmetry. Predicted to be located in axoneme. Predicted to be part of outer dynein arm. Implicated in primary ciliary dyskinesia 17. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr17-44902549-A-C is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.1718575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC103	NM_213607.3	c.461A>G	p.His154Arg	missense_variant	Exon 4 of 4	ENST00000417826.3	NP_998772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC103	ENST00000417826.3	c.461A>G	p.His154Arg	missense_variant	Exon 4 of 4	1	NM_213607.3	ENSP00000391692.2
CCDC103	ENST00000410006.6	c.461A>G	p.His154Arg	missense_variant	Exon 4 of 4	2		ENSP00000387252.1
CCDC103	ENST00000357776.6	c.461A>G	p.His154Arg	missense_variant	Exon 4 of 4	2		ENSP00000350420.2
CCDC103	ENST00000410027.5	c.*211A>G		downstream_gene_variant		4		ENSP00000386640.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727246

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.052	T;.;T;.
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.066
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.65	.;T;.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.5	M;.;M;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	N;N;N;.
REVEL	Benign	0.12
Sift	Benign	0.053	T;T;T;.
Sift4G	Benign	0.23	T;T;T;T
Polyphen		0.47	P;.;P;.
Vest4		0.35
MutPred		0.36		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.51
MPC		0.39
ClinPred		0.36	T
GERP RS		5.6
Varity_R		0.26
gMVP		0.47

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-42979917;