16-84155693-C-G

Variant names:

• chr16-84155693-C-G
• NM_178452.6:c.685C>G

Variant summary

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

The NM_178452.6(DNAAF1):​c.685C>G​(p.His229Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAAF1 NM_178452.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6	c.685C>G	p.His229Asp	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.685C>G	p.His229Asp	missense_variant	Exon 5 of 12	1	NM_178452.6	ENSP00000367815.5
DNAAF1	ENST00000567918.5	n.685C>G		non_coding_transcript_exon_variant	Exon 5 of 7	1		ENSP00000455154.1
DNAAF1	ENST00000563093.5	n.685C>G		non_coding_transcript_exon_variant	Exon 5 of 11	2		ENSP00000457373.1
DNAAF1	ENST00000570298.5	n.839C>G		non_coding_transcript_exon_variant	Exon 5 of 11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.012
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-7.6	D
REVEL	Benign	0.14
Sift	Benign	0.054	T
Sift4G	Uncertain	0.024	D
Polyphen		0.11	B
Vest4		0.73
MutPred		0.43		Gain of disorder (P = 0.0682);
MVP		0.39
MPC		0.032
ClinPred		0.93	D
GERP RS		3.1
Varity_R		0.43
gMVP		0.76

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: chr16-84189298;