Genetic Variant ENST00000567918.5:n.-83dupT (chr16-84145225-A-AC) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000567918.5(DNAAF1):n.-216_-215insC variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000964 in 518,664 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

DNAAF1
ENST00000567918.5 upstream_gene

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0410

Publications

0 publications found

Variant links:

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 links:

HSDL1 (HGNC:16475): (hydroxysteroid dehydrogenase like 1) Predicted to enable oxidoreductase activity. Located in intermediate filament cytoskeleton and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

HSDL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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 link	c.-216_-215insC		upstream_gene_variant		ENST00000378553.10	NP_848547.4	Q8NEP3-1A0A140VJN4
HSDL1	NM_031463.5 link	c.-215_-214insG		upstream_gene_variant		ENST00000219439.9	NP_113651.4	Q3SXM5-1I6L975

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10 link	c.-216_-215insC		upstream_gene_variant		1	NM_178452.6	ENSP00000367815.5		Q8NEP3-1
HSDL1	ENST00000219439.9 link	c.-215_-214insG		upstream_gene_variant		1	NM_031463.5	ENSP00000219439.4		Q3SXM5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000964

AC:

AN:

518664

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

266548

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10874

American (AMR)

AF:

0.000190

AC:

AN:

15772

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12074

East Asian (EAS)

AF:

0.00

AC:

AN:

24238

South Asian (SAS)

AF:

0.00

AC:

AN:

44014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1926

European-Non Finnish (NFE)

AF:

0.00000558

AC:

AN:

358176

Other (OTH)

AF:

0.00

AC:

AN:

26602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.041

Splicing

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

Publications

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ENST00000567918.5:n.-83dupT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over