chr16-84145295-G-C

Variant names:

• chr16-84145295-G-C
• rs886052362
• ENST00000570298.5:n.9G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000570298.5(DNAAF1):​n.9G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000408 in 1,226,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: DNAAF1 ENST00000570298.5 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.856
• Publications: 0 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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6	c.-146G>C		upstream_gene_variant		ENST00000378553.10	NP_848547.4
HSDL1	NM_031463.5	c.-284C>G		upstream_gene_variant		ENST00000219439.9	NP_113651.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF1	ENST00000378553.10	c.-146G>C		upstream_gene_variant		1	NM_178452.6	ENSP00000367815.5
HSDL1	ENST00000219439.9	c.-284C>G		upstream_gene_variant		1	NM_031463.5	ENSP00000219439.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000408 AC: 5 AN: 1226370 Hom.: 0 Cov.: 17 AF XY: 0.00000662 AC XY: 4 AN XY: 604196

African (AFR) AF: 0.00 AC: 0 AN: 27782

American (AMR) AF: 0.00 AC: 0 AN: 31718

Ashkenazi Jewish (ASJ) AF: 0.000220 AC: 5 AN: 22690

East Asian (EAS) AF: 0.00 AC: 0 AN: 33908

South Asian (SAS) AF: 0.00 AC: 0 AN: 72824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 948950

Other (OTH) AF: 0.00 AC: 0 AN: 51914

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.49
PhyloP100		-0.86
PromoterAI		-0.019	Neutral

Splicing

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

Other links and lift over

dbSNP: rs886052362; hg19: chr16-84178900;