19-55159145-C-A

Variant names:

• chr19-55159145-C-A
• NM_001256715.2:c.1543G>T

Variant summary

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

The NM_001256715.2(DNAAF3):​c.1543G>T​(p.Gly515Cys) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G515S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAAF3 NM_001256715.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

Genes affected

DNAAF3 (HGNC:30492): (dynein axonemal assembly factor 3) The protein encoded by this gene is required for the assembly of axonemal inner and outer dynein arms and plays a role in assembling dynein complexes for transport into cilia. Defects in this gene are a cause of primary ciliary dyskinesia type 2 (CILD2). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

ENSG00000267110 (HGNC:):

DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

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=0.1395585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF3	NM_001256715.2	c.1543G>T	p.Gly515Cys	missense_variant	Exon 12 of 12	ENST00000524407.7	NP_001243644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF3	ENST00000524407.7	c.1543G>T	p.Gly515Cys	missense_variant	Exon 12 of 12	1	NM_001256715.2	ENSP00000432046.3
ENSG00000267110	ENST00000587871.1	n.478+48G>T		intron_variant	Intron 4 of 8	5		ENSP00000473050.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0040	.;T;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.44	T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;N;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.2	N;.;.;N
REVEL	Benign	0.099
Sift	Uncertain	0.016	D;.;.;D
Sift4G	Uncertain	0.058	T;T;T;T
Polyphen		0.95	.;P;.;.
Vest4		0.15
MutPred		0.19		.;Gain of catalytic residue at P514 (P = 0.0072);.;.;
MVP		0.19
MPC		0.79
ClinPred		0.60	D
GERP RS		1.8
Varity_R		0.089
gMVP		0.27

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: chr19-55670513;