20-3259973-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.77
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27397794).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAAF9NM_001009984.3 linkc.2929G>A p.Val977Ile missense_variant Exon 32 of 37 ENST00000252032.10 NP_001009984.1 Q5TEA3Q0IIP3
DNAAF9XM_005260684.5 linkc.2926G>A p.Val976Ile missense_variant Exon 32 of 37 XP_005260741.1
DNAAF9XM_005260687.6 linkc.1174G>A p.Val392Ile missense_variant Exon 13 of 18 XP_005260744.1
DNAAF9XM_011529208.4 linkc.1174G>A p.Val392Ile missense_variant Exon 13 of 18 XP_011527510.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAAF9ENST00000252032.10 linkc.2929G>A p.Val977Ile missense_variant Exon 32 of 37 5 NM_001009984.3 ENSP00000252032.9 Q5TEA3

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152238
Hom.:
0
Cov.:
33
show subpopulations
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
GnomAD3 exomes
AF:
0.000128
AC:
32
AN:
249550
Hom.:
0
AF XY:
0.000126
AC XY:
17
AN XY:
135390
show subpopulations
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 SAS exome
AF:
0.0000327
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.000322
Gnomad4 OTH exome
AF:
0.000530
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152238
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000241
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

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 12, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2929G>A (p.V977I) alteration is located in exon 32 (coding exon 32) of the C20orf194 gene. This alteration results from a G to A substitution at nucleotide position 2929, causing the valine (V) at amino acid position 977 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
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

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs182286470; hg19: chr20-3240619; API