X-48478618-G-T

Variant names:

• chrX-48478618-G-T
• rs782360834
• NM_012280.4:c.193G>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_012280.4(FTSJ1):​c.193G>T​(p.Gly65Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000912 in 1,205,757 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000082 (0 hom. 3 hem.)
• Consequence: FTSJ1 NM_012280.4 missense, splice_region
• Scores: Splicing: ADA: 0.0003124
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.929

Genes affected

FTSJ1 (HGNC:13254): (FtsJ RNA 2'-O-methyltransferase 1) This gene encodes a member of the methyltransferase superfamily. The encoded protein localizes to the nucleolus, binds to S-adenosylmethionine, and may be involved in the processing and modification of ribosomal RNA. Mutations in this gene are associated with cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2325713).
• BS2: High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTSJ1	NM_012280.4	c.193G>T	p.Gly65Cys	missense_variant, splice_region_variant	Exon 4 of 13	ENST00000348411.3	NP_036412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTSJ1	ENST00000348411.3	c.193G>T	p.Gly65Cys	missense_variant, splice_region_variant	Exon 4 of 13	1	NM_012280.4	ENSP00000326948.2

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111761 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33923

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000377

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000823 AC: 9 AN: 1093996 Hom.: 0 Cov.: 30 AF XY: 0.00000834 AC XY: 3 AN XY: 359568

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: 0.0000107

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111761 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33923

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000377

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	.;T
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.027	D;D
Sift4G	Uncertain	0.042	D;D
Polyphen		0.0010	B;P
Vest4		0.32
MutPred		0.56		Loss of disorder (P = 0.0063);Loss of disorder (P = 0.0063);
MVP		0.34
MPC		1.3
ClinPred		0.86	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00031
dbscSNV1_RF	Benign	0.066
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

Other links and lift over

dbSNP: rs782360834; hg19: chrX-48337006;