rs368687225

Variant names:

• chr20-3376273-C-A
• rs368687225
• NM_001009984.3:c.313G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-3376273-C-A
• chr20-3376273-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001009984.3(DNAAF9):​c.313G>T​(p.Val105Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,458,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V105I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAAF9 NM_001009984.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.827

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009984.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF9	NM_001009984.3	MANE Select	c.313G>T	p.Val105Phe	missense	Exon 4 of 37	NP_001009984.1	Q5TEA3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF9	ENST00000252032.10	TSL:5 MANE Select	c.313G>T	p.Val105Phe	missense	Exon 4 of 37	ENSP00000252032.9	Q5TEA3
	DNAAF9	ENST00000851200.1		c.313G>T	p.Val105Phe	missense	Exon 4 of 37	ENSP00000521259.1
	DNAAF9	ENST00000953496.1		c.313G>T	p.Val105Phe	missense	Exon 4 of 37	ENSP00000623555.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458850 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725900

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 85798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110090

Other (OTH) AF: 0.00 AC: 0 AN: 60272

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.8
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.95
MutPred		0.40		Loss of stability (P = 0.0256)
MVP		0.71
MPC		0.80
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.62
gMVP		0.82
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs368687225; hg19: chr20-3356920;