20-3376273-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001009984.3(DNAAF9):​c.313G>A​(p.Val105Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000577 in 1,611,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000054 (0 hom.)
• Consequence: DNAAF9 NM_001009984.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.80
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07555398).

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>A	p.Val105Ile	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>A	p.Val105Ile	missense	Exon 4 of 37	ENSP00000252032.9	Q5TEA3
	DNAAF9	ENST00000851200.1		c.313G>A	p.Val105Ile	missense	Exon 4 of 37	ENSP00000521259.1
	DNAAF9	ENST00000953496.1		c.313G>A	p.Val105Ile	missense	Exon 4 of 37	ENSP00000623555.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000109 AC: 27 AN: 247848 AF XY: 0.0000892

Gnomad AFR exome AF: 0.0000648

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.0000997

Gnomad EAS exome AF: 0.000837

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000542 AC: 79 AN: 1458850 Hom.: 0 Cov.: 28 AF XY: 0.0000551 AC XY: 40 AN XY: 725900

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

American (AMR) AF: 0.000135 AC: 6 AN: 44454

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26080

East Asian (EAS) AF: 0.000984 AC: 39 AN: 39624

South Asian (SAS) AF: 0.0000932 AC: 8 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: 0.0000189 AC: 21 AN: 1110090

Other (OTH) AF: 0.0000664 AC: 4 AN: 60272

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74446

African (AFR) AF: 0.0000241 AC: 1 AN: 41536

American (AMR) AF: 0.000261 AC: 4 AN: 15300

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

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68026

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000107 Hom.: 0

Bravo AF: 0.0000831

ESP6500AA AF: 0.000269 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000662 AC: 8

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.11
Eigen_PC	Benign	0.014
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.8
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.083
Sift	Benign	0.12	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.24	B
Vest4		0.23
MVP		0.44
MPC		0.20
ClinPred		0.063	T
GERP RS		4.5
Varity_R		0.062
gMVP		0.35
Mutation Taster		=92/8	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; COSMIC: COSV52703776;