Genetic Variant DNAAF1:c.-197G>T (chr16-84145244-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_178452.6(DNAAF1):c.-197G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 855,618 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0063 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00067 ( 12 hom. )

Consequence

DNAAF1
NM_178452.6 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.31

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00626 (952/152118) while in subpopulation AFR AF = 0.0215 (893/41530). AF 95% confidence interval is 0.0203. There are 14 homozygotes in GnomAd4. There are 445 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF1	NM_178452.6 link	c.-197G>T		upstream_gene_variant		ENST00000378553.10	NP_848547.4	Q8NEP3-1A0A140VJN4
HSDL1	NM_031463.5 link	c.-233C>A		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.-197G>T		upstream_gene_variant		1	NM_178452.6	ENSP00000367815.5		Q8NEP3-1
HSDL1	ENST00000219439.9 link	c.-233C>A		upstream_gene_variant		1	NM_031463.5	ENSP00000219439.4		Q3SXM5-1

Frequencies

GnomAD3 genomes

AF:

0.00626

AC:

951

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00574

GnomAD4 exome

AF:

0.000667

AC:

469

AN:

703500

Hom.:

Cov.:

AF XY:

0.000599

AC XY:

213

AN XY:

355376

show subpopulations

African (AFR)

AF:

0.0244

AC:

380

AN:

15546

American (AMR)

AF:

0.00125

AC:

AN:

20060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14634

East Asian (EAS)

AF:

0.00

AC:

AN:

28224

South Asian (SAS)

AF:

0.0000198

AC:

AN:

50604

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27414

Middle Eastern (MID)

AF:

0.00167

AC:

AN:

2402

European-Non Finnish (NFE)

AF:

0.0000196

AC:

AN:

511014

Other (OTH)

AF:

0.00146

AC:

AN:

33602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00626

AC:

952

AN:

152118

Hom.:

Cov.:

AF XY:

0.00598

AC XY:

445

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0215

AC:

893

AN:

41530

American (AMR)

AF:

0.00288

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67948

Other (OTH)

AF:

0.00568

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

140

187

234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00485

Hom.:

Bravo

AF:

0.00723

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.7

(source)

DANN

Benign

0.45

PhyloP100

1.3

PromoterAI

-0.14

Neutral

(source)

Splicing

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

Publications

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16-84145244-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over