17-63820415-C-T

Variant names:

• chr17-63820415-C-T
• NM_017647.4:c.2096G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017647.4(FTSJ3):​c.2096G>A​(p.Gly699Glu) 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: 31)
• Consequence: FTSJ3 NM_017647.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.616

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]

ACMG classification

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=0.037064612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTSJ3	NM_017647.4	c.2096G>A	p.Gly699Glu	missense_variant	Exon 19 of 21	ENST00000427159.7	NP_060117.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTSJ3	ENST00000427159.7	c.2096G>A	p.Gly699Glu	missense_variant	Exon 19 of 21	1	NM_017647.4	ENSP00000396673.2
FTSJ3	ENST00000583202.5	n.752G>A		non_coding_transcript_exon_variant	Exon 5 of 5	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2096G>A (p.G699E) 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 2096, causing the glycine (G) at amino acid position 699 to be replaced by a glutamic acid (E). 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	0.086
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.73
DEOGEN2	Benign	0.00077	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.58	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.35	N
REVEL	Benign	0.011
Sift	Benign	0.56	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.28
MutPred		0.36		Loss of sheet (P = 0.0181);
MVP		0.061
MPC		0.14
ClinPred		0.047	T
GERP RS		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.034
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-61897775;