X-48478630-G-T

Position:

• chrX-48478630-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012280.4(FTSJ1):​c.205G>T​(p.Gly69Cys) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: FTSJ1 NM_012280.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.843

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27343383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTSJ1	NM_012280.4	c.205G>T	p.Gly69Cys	missense_variant	4/13	ENST00000348411.3	NP_036412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTSJ1	ENST00000348411.3	c.205G>T	p.Gly69Cys	missense_variant	4/13	1	NM_012280.4	ENSP00000326948	P4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

History of neurodevelopmental disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2017

There is insufficient or conflicting evidence for classification of this alteration. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.20	.;T
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.28	N;N
REVEL	Benign	0.057
Sift	Benign	0.061	T;T
Sift4G	Uncertain	0.056	T;T
Polyphen		0.017	B;P
Vest4		0.45
MutPred		0.76		Loss of disorder (P = 0.0187);Loss of disorder (P = 0.0187);
MVP		0.42
MPC		0.77
ClinPred		0.33	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.81

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

Other links and lift over

dbSNP: rs782012239; hg19: chrX-48337018;