chr20-3259973-C-T

Variant names:

• chr20-3259973-C-T
• rs182286470
• NM_001009984.3:c.2929G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001009984.3(DNAAF9):​c.2929G>A​(p.Val977Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000263 in 1,613,022 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00027 (1 hom.)
• Consequence: DNAAF9 NM_001009984.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.77
• Publications: 5 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.27397794).

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.2929G>A	p.Val977Ile	missense	Exon 32 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.2929G>A	p.Val977Ile	missense	Exon 32 of 37	ENSP00000252032.9	Q5TEA3
	DNAAF9	ENST00000851200.1		c.2926G>A	p.Val976Ile	missense	Exon 32 of 37	ENSP00000521259.1
	DNAAF9	ENST00000953496.1		c.2863G>A	p.Val955Ile	missense	Exon 32 of 37	ENSP00000623555.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000128 AC: 32 AN: 249550 AF XY: 0.000126

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000221

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000274 AC: 400 AN: 1460784 Hom.: 1 Cov.: 29 AF XY: 0.000264 AC XY: 192 AN XY: 726832

African (AFR) AF: 0.0000598 AC: 2 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39694

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86242

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000322 AC: 358 AN: 1111010

Other (OTH) AF: 0.000530 AC: 32 AN: 60356

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152238 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74372

African (AFR) AF: 0.000121 AC: 5 AN: 41470

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000239 Hom.: 0

Bravo AF: 0.000159

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000262 AC: 1

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.000141 AC: 17

EpiCase AF: 0.000273

EpiControl AF: 0.000356

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	0.091
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.8
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.17
Sift	Benign	0.36	T
Sift4G	Uncertain	0.058	T
Polyphen		1.0	D
Vest4		0.43
MVP		0.26
MPC		0.64
ClinPred		0.12	T
GERP RS		5.2
Varity_R		0.094
gMVP		0.28
Mutation Taster		=95/5	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: rs182286470; hg19: chr20-3240619;