NM_213607.3:c.31G>A

Variant names:

• chr17-44901029-G-A
• rs146015856
• NM_213607.3:c.31G>A

Variant summary

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

The NM_213607.3(CCDC103):​c.31G>A​(p.Ala11Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC103 NM_213607.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

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=0.16943282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC103	NM_213607.3	c.31G>A	p.Ala11Thr	missense_variant	Exon 2 of 4	ENST00000417826.3	NP_998772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC103	ENST00000417826.3	c.31G>A	p.Ala11Thr	missense_variant	Exon 2 of 4	1	NM_213607.3	ENSP00000391692.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.061	.;T;.;.;T;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.62	T;.;T;T;.;T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.17	T;T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.4	.;M;.;M;M;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.4	.;N;N;N;N;.
REVEL	Benign	0.20
Sift	Benign	0.097	.;T;T;T;T;.
Sift4G	Benign	0.17	T;T;T;T;T;T
Polyphen		0.81	.;P;.;.;P;.
Vest4		0.19, 0.19, 0.20
MutPred		0.22		Gain of phosphorylation at A11 (P = 0.0747);Gain of phosphorylation at A11 (P = 0.0747);Gain of phosphorylation at A11 (P = 0.0747);Gain of phosphorylation at A11 (P = 0.0747);Gain of phosphorylation at A11 (P = 0.0747);Gain of phosphorylation at A11 (P = 0.0747);
MVP		0.72
MPC		0.37
ClinPred		0.43	T
GERP RS		3.7
Varity_R		0.043
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs146015856; hg19: chr17-42978397;