16-84170131-G-C

Position:

• chr16-84170131-G-C

Variant summary

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

The NM_178452.6(DNAAF1):​c.1303G>C​(p.Asp435His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,438,164 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D435N) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DNAAF1 NM_178452.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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 (HGNC:):

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=0.18052202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF1	NM_178452.6	c.1303G>C	p.Asp435His	missense_variant	8/12	ENST00000378553.10	NP_848547.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10	c.1303G>C	p.Asp435His	missense_variant	8/12	1	NM_178452.6	ENSP00000367815.5
DNAAF1	ENST00000563818.5	n.980G>C		non_coding_transcript_exon_variant	4/8	2
DNAAF1	ENST00000570298.5	n.1457G>C		non_coding_transcript_exon_variant	8/11	2
DNAAF1	ENST00000563093.5	n.1225+78G>C		intron_variant		2		ENSP00000457373.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1438164 Hom.: 0 Cov.: 97 AF XY: 0.00 AC XY: 0 AN XY: 714870

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: 9.10e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.061
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.075	T
Polyphen		0.97	D
Vest4		0.080
MutPred		0.16		Gain of methylation at K430 (P = 0.1482);
MVP		0.29
MPC		0.14
ClinPred		0.25	T
GERP RS		1.2
Varity_R		0.074
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs149158199; hg19: chr16-84203737;