17-63820367-C-T

Variant summary

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

The NM_017647.4(FTSJ3):​c.2144G>A​(p.Arg715Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

FTSJ3
NM_017647.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.444
Variant links:
Genes affected
FTSJ3 (HGNC:17136): (FtsJ RNA 2'-O-methyltransferase 3) Although the function of this gene is not known, the existence of this gene is supported by mRNA and EST data. A possible function of the encoded protein can be inferred from amino acid sequence similarity to the E.coli FtsJ protein and to a mouse protein possibly involved in embryogenesis. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.12477538).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FTSJ3NM_017647.4 linkc.2144G>A p.Arg715Gln missense_variant Exon 19 of 21 ENST00000427159.7 NP_060117.3 Q8IY81

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FTSJ3ENST00000427159.7 linkc.2144G>A p.Arg715Gln missense_variant Exon 19 of 21 1 NM_017647.4 ENSP00000396673.2 Q8IY81
FTSJ3ENST00000583202.5 linkn.800G>A non_coding_transcript_exon_variant Exon 5 of 5 3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251490
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461882
Hom.:
0
Cov.:
35
AF XY:
0.00000963
AC XY:
7
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000282
Hom.:
0
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 29, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2144G>A (p.R715Q) alteration is located in exon 19 (coding exon 18) of the FTSJ3 gene. This alteration results from a G to A substitution at nucleotide position 2144, causing the arginine (R) at amino acid position 715 to be replaced by a glutamine (Q). 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
0.092
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.47
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0054
T
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.63
FATHMM_MKL
Benign
0.20
N
LIST_S2
Uncertain
0.90
D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.92
N
REVEL
Benign
0.049
Sift
Benign
0.042
D
Sift4G
Benign
0.10
T
Polyphen
0.77
P
Vest4
0.40
MutPred
0.39
Loss of MoRF binding (P = 0.0291);
MVP
0.16
MPC
0.31
ClinPred
0.52
D
GERP RS
2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.081
gMVP
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1294267154; hg19: chr17-61897727; API