rs139743343

Variant names:

• chr16-84155627-C-A
• rs139743343
• NM_178452.6:c.619C>A

Your query was ambiguous. Multiple possible variants found:

• chr16-84155627-C-A
• chr16-84155627-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_178452.6(DNAAF1):​c.619C>A​(p.Leu207Met) 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 pathogenic 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. L207V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAAF1 NM_178452.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 3 publications found

Genes affected

DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DNAAF1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 13

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6	c.619C>A	p.Leu207Met	missense_variant	Exon 5 of 12	ENST00000378553.10	NP_848547.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10	c.619C>A	p.Leu207Met	missense_variant	Exon 5 of 12	1	NM_178452.6	ENSP00000367815.5
DNAAF1	ENST00000567918.5	n.619C>A		non_coding_transcript_exon_variant	Exon 5 of 7	1		ENSP00000455154.1
DNAAF1	ENST00000563093.5	n.619C>A		non_coding_transcript_exon_variant	Exon 5 of 11	2		ENSP00000457373.1
DNAAF1	ENST00000570298.5	n.773C>A		non_coding_transcript_exon_variant	Exon 5 of 11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.0077
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		0.18
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.68		Gain of disorder (P = 0.102);
MVP		0.37
MPC		0.16
ClinPred		0.95	D
GERP RS		0.080
Varity_R		0.47
gMVP		0.51
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs139743343; hg19: chr16-84189232;