20-3147141-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021826.5(FASTKD5):​c.1930G>T​(p.Gly644Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

FASTKD5
NM_021826.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.167
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)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13976315).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FASTKD5NM_021826.5 linkc.1930G>T p.Gly644Cys missense_variant Exon 2 of 2 ENST00000380266.4 NP_068598.1 Q7L8L6
UBOX5NM_014948.4 linkc.-42+12625G>T 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.1930G>T p.Gly644Cys missense_variant Exon 2 of 2 1 NM_021826.5 ENSP00000369618.3 Q7L8L6
UBOX5ENST00000217173.7 linkc.-42+12625G>T intron_variant Intron 1 of 4 1 NM_014948.4 ENSP00000217173.2 O94941-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 06, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1930G>T (p.G644C) alteration is located in exon 2 (coding exon 1) of the FASTKD5 gene. This alteration results from a G to T substitution at nucleotide position 1930, causing the glycine (G) at amino acid position 644 to be replaced by a cysteine (C). 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
0.15
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.018
T
Eigen
Benign
-0.083
Eigen_PC
Benign
-0.11
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.45
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.94
N
REVEL
Benign
0.088
Sift
Uncertain
0.018
D
Sift4G
Uncertain
0.016
D
Polyphen
0.99
D
Vest4
0.33
MutPred
0.39
Loss of loop (P = 0.0073);
MVP
0.42
MPC
0.27
ClinPred
0.57
D
GERP RS
3.5
Varity_R
0.093
gMVP
0.31

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: rs2066572871; hg19: chr20-3127787; API