16-84145552-G-T

Position:

• chr16-84145552-G-T

Variant summary

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

The ENST00000378553.10(DNAAF1):​c.112G>T​(p.Gly38Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,562 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. G38A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: DNAAF1 ENST00000378553.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1186212).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAAF1	NM_178452.6	c.112G>T	p.Gly38Cys	missense_variant	1/12	ENST00000378553.10	NP_848547.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10	c.112G>T	p.Gly38Cys	missense_variant	1/12	1	NM_178452.6	ENSP00000367815	P1
DNAAF1	ENST00000567918.5	c.112G>T	p.Gly38Cys	missense_variant, NMD_transcript_variant	1/7	1		ENSP00000455154
DNAAF1	ENST00000570298.5	n.266G>T		non_coding_transcript_exon_variant	1/11	2
DNAAF1	ENST00000563093.5	c.112G>T	p.Gly38Cys	missense_variant, NMD_transcript_variant	1/11	2		ENSP00000457373

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396562 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 688968

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0058	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.083
Sift	Benign	0.092	T
Sift4G	Benign	0.21	T
Polyphen		0.92	P
Vest4		0.21
MVP		0.23
MPC		0.076
ClinPred		0.42	T
GERP RS		-0.93
Varity_R		0.13
gMVP		0.22

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: rs551990619; hg19: chr16-84179157;