20-3374581-T-G

Variant names:

• chr20-3374581-T-G
• rs750702
• NM_001009984.3:c.506-427A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001009984.3(DNAAF9):​c.506-427A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,220 control chromosomes in the GnomAD database, including 4,021 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 0.20 (4021 hom., cov: 33)
• Consequence: DNAAF9 NM_001009984.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

Genes affected

DNAAF9 (HGNC:17721): (dynein axonemal assembly factor 9) This gene encodes an uncharacterized protein with a C-terminal coiled-coil region. The gene is located on chromosome 20p13 in a 1.8 Mb region linked to a spinocerebellar ataxia phenotype, but this gene does not appear to be a disease candidate. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF9	NM_001009984.3	c.506-427A>C		intron_variant	Intron 5 of 36	ENST00000252032.10	NP_001009984.1
DNAAF9	XM_005260684.5	c.506-427A>C		intron_variant	Intron 5 of 36		XP_005260741.1
DNAAF9	XM_047440081.1	c.506-427A>C		intron_variant	Intron 5 of 25		XP_047296037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF9	ENST00000252032.10	c.506-427A>C		intron_variant	Intron 5 of 36	5	NM_001009984.3	ENSP00000252032.9

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31084 AN: 152102 Hom.: 4009 Cov.: 33

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.214

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.204 AC: 31114 AN: 152220 Hom.: 4021 Cov.: 33 AF XY: 0.206 AC XY: 15341 AN XY: 74400

Gnomad4 AFR AF: 0.0510

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.242

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.219

Alfa AF: 0.185 Hom.: 675

Bravo AF: 0.197

Asia WGS AF: 0.396 AC: 1375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.78

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: rs750702; hg19: chr20-3355228;