20-3147039-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021826.5(FASTKD5):​c.2032G>A​(p.Ala678Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

FASTKD5
NM_021826.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.503
Variant links:
Genes affected
FASTKD5 (HGNC:25790): (FAST kinase domains 5) Enables rRNA binding activity. Involved in mitochondrial RNA processing. Located in mitochondrial nucleoid and ribonucleoprotein granule. [provided by Alliance of Genome Resources, Apr 2022]
UBOX5 (HGNC:17777): (U-box domain containing 5) This gene encodes a U-box domain containing protein. The encoded protein interacts with E2 enzymes and may play a role in the ubiquitination pathway. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]
UBOX5-AS1 (HGNC:44111): (UBOX5 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03823781).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FASTKD5NM_021826.5 linkc.2032G>A p.Ala678Thr missense_variant Exon 2 of 2 ENST00000380266.4 NP_068598.1 Q7L8L6
UBOX5NM_014948.4 linkc.-42+12727G>A intron_variant Intron 1 of 4 ENST00000217173.7 NP_055763.1 O94941-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FASTKD5ENST00000380266.4 linkc.2032G>A p.Ala678Thr missense_variant Exon 2 of 2 1 NM_021826.5 ENSP00000369618.3 Q7L8L6
UBOX5ENST00000217173.7 linkc.-42+12727G>A intron_variant Intron 1 of 4 1 NM_014948.4 ENSP00000217173.2 O94941-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
251316
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135836
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461884
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2032G>A (p.A678T) alteration is located in exon 2 (coding exon 1) of the FASTKD5 gene. This alteration results from a G to A substitution at nucleotide position 2032, causing the alanine (A) at amino acid position 678 to be replaced by a threonine (T). 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
0.071
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.30
DANN
Benign
0.52
DEOGEN2
Benign
0.0073
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.40
T
M_CAP
Benign
0.0047
T
MetaRNN
Benign
0.038
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.7
L
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.26
N
REVEL
Benign
0.0030
Sift
Benign
0.90
T
Sift4G
Benign
0.54
T
Polyphen
0.010
B
Vest4
0.035
MutPred
0.32
Gain of helix (P = 0.062);
MVP
0.12
MPC
0.070
ClinPred
0.016
T
GERP RS
-2.6
Varity_R
0.018
gMVP
0.16

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: rs776236377; hg19: chr20-3127685; API