17-44901557-C-G

Variant names:

• chr17-44901557-C-G
• rs763938078
• NM_213607.3:c.181C>G

Variant summary

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

The NM_213607.3(CCDC103):​c.181C>G​(p.Arg61Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC103 NM_213607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24203181).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC103	NM_213607.3	c.181C>G	p.Arg61Gly	missense_variant	Exon 3 of 4	ENST00000417826.3	NP_998772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC103	ENST00000417826.3	c.181C>G	p.Arg61Gly	missense_variant	Exon 3 of 4	1	NM_213607.3	ENSP00000391692.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251482 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135920

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;.;.;T;.
Eigen	Benign	-0.052
Eigen_PC	Benign	-0.0093
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.77	.;T;T;.;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.6	M;.;M;M;.
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-4.1	D;D;D;D;.
REVEL	Benign	0.22
Sift	Uncertain	0.0060	D;D;D;D;.
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		0.59	P;.;.;P;.
Vest4		0.15
MutPred		0.27		Loss of MoRF binding (P = 0.0055);Loss of MoRF binding (P = 0.0055);Loss of MoRF binding (P = 0.0055);Loss of MoRF binding (P = 0.0055);Loss of MoRF binding (P = 0.0055);
MVP		0.74
MPC		0.69
ClinPred		0.93	D
GERP RS		3.4
Varity_R		0.25
gMVP		0.17

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

LitVar

Other links and lift over

dbSNP: rs763938078; hg19: chr17-42978925;