17-44901029-G-T

Variant names:

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

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>T​(p.Ala11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,842 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.

• 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: 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=0.119432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC103	NM_213607.3	c.31G>T	p.Ala11Ser	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>T	p.Ala11Ser	missense_variant	Exon 2 of 4	1	NM_213607.3	ENSP00000391692.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450842 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721946

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: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	.;T;.;.;T;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.80	T;.;T;T;.;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.12	T;T;T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.1	.;M;.;M;M;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.29	.;N;N;N;N;.
REVEL	Benign	0.14
Sift	Benign	0.13	.;T;T;T;T;.
Sift4G	Benign	0.35	T;T;T;T;T;T
Polyphen		0.39	.;B;.;.;B;.
Vest4		0.19, 0.20
MutPred		0.25		Gain of phosphorylation at A11 (P = 0.0629);Gain of phosphorylation at A11 (P = 0.0629);Gain of phosphorylation at A11 (P = 0.0629);Gain of phosphorylation at A11 (P = 0.0629);Gain of phosphorylation at A11 (P = 0.0629);Gain of phosphorylation at A11 (P = 0.0629);
MVP		0.65
MPC		0.18
ClinPred		0.18	T
GERP RS		3.7
Varity_R		0.042
gMVP		0.25

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: chr17-42978397;