17-63819809-C-G

Variant names:

• chr17-63819809-C-G
• NM_017647.4:c.2537G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017647.4(FTSJ3):​c.2537G>C​(p.Arg846Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,068 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: FTSJ3 NM_017647.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTSJ3	NM_017647.4	c.2537G>C	p.Arg846Pro	missense_variant	Exon 21 of 21	ENST00000427159.7	NP_060117.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTSJ3	ENST00000427159.7	c.2537G>C	p.Arg846Pro	missense_variant	Exon 21 of 21	1	NM_017647.4	ENSP00000396673.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460068 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726286

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2537G>C (p.R846P) alteration is located in exon 21 (coding exon 20) of the FTSJ3 gene. This alteration results from a G to C substitution at nucleotide position 2537, causing the arginine (R) at amino acid position 846 to be replaced by a proline (P). 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	0.25
BayesDel_addAF	Benign	-0.0098	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Benign	0.92
DEOGEN2	Benign	0.0087	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.14
Sift	Benign	0.034	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.27		Gain of glycosylation at R846 (P = 0.0054);
MVP		0.55
MPC		0.16
ClinPred		0.62	D
GERP RS		4.7
Varity_R		0.41
gMVP		0.050

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: chr17-61897169;