16-84145422-C-T

Variant names:

• chr16-84145422-C-T
• rs369581422
• NM_178452.6:c.-19C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_178452.6(DNAAF1):​c.-19C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000451 in 1,575,556 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (1 hom.)
• Consequence: DNAAF1 NM_178452.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0750

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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 16-84145422-C-T is Benign according to our data. Variant chr16-84145422-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262934.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.0000372 (53/1423226) while in subpopulation AFR AF = 0.000967 (32/33084). AF 95% confidence interval is 0.000703. There are 1 homozygotes in GnomAdExome4. There are 34 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6	c.-19C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12	ENST00000378553.10	NP_848547.4
DNAAF1	NM_178452.6	c.-19C>T		5_prime_UTR_variant	Exon 1 of 12	ENST00000378553.10	NP_848547.4
HSDL1	NM_031463.5	c.-411G>A		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.-19C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12	1	NM_178452.6	ENSP00000367815.5
DNAAF1	ENST00000378553.10	c.-19C>T		5_prime_UTR_variant	Exon 1 of 12	1	NM_178452.6	ENSP00000367815.5
HSDL1	ENST00000219439.9	c.-411G>A		upstream_gene_variant		1	NM_031463.5	ENSP00000219439.4

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000427 AC: 8 AN: 187234 AF XY: 0.00000997

Gnomad AFR exome AF: 0.000601

Gnomad AMR exome AF: 0.0000368

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000372 AC: 53 AN: 1423226 Hom.: 1 Cov.: 31 AF XY: 0.0000483 AC XY: 34 AN XY: 704226

African (AFR) AF: 0.000967 AC: 32 AN: 33084

American (AMR) AF: 0.0000525 AC: 2 AN: 38128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25274

East Asian (EAS) AF: 0.00 AC: 0 AN: 38292

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49930

Middle Eastern (MID) AF: 0.000702 AC: 4 AN: 5702

European-Non Finnish (NFE) AF: 0.00000458 AC: 5 AN: 1092896

Other (OTH) AF: 0.000153 AC: 9 AN: 59014

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152330 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74496

African (AFR) AF: 0.000433 AC: 18 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000121

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.9
DANN	Benign	0.87
PhyloP100		-0.075
PromoterAI		0.019	Neutral

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

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Other links and lift over

dbSNP: rs369581422; hg19: chr16-84179027;