NM_012280.4:c.111A>G

Variant names:

• chrX-48478158-A-G
• rs1556967000
• NM_012280.4:c.111A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_012280.4(FTSJ1):​c.111A>G​(p.Gln37Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000183 in 1,094,442 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts 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: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 2 hem.)
• Consequence: FTSJ1 NM_012280.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 0 publications found

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]

FTSJ1 Gene-Disease associations (from GenCC):

• intellectual disability, X-linked 9

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-2.62 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012280.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTSJ1	NM_012280.4	MANE Select	c.111A>G	p.Gln37Gln	synonymous	Exon 2 of 13	NP_036412.1	A0A024QYX5
	FTSJ1	NM_001441197.1		c.111A>G	p.Gln37Gln	synonymous	Exon 2 of 11	NP_001428126.1
	FTSJ1	NM_001441198.1		c.111A>G	p.Gln37Gln	synonymous	Exon 3 of 12	NP_001428127.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTSJ1	ENST00000348411.3	TSL:1 MANE Select	c.111A>G	p.Gln37Gln	synonymous	Exon 2 of 13	ENSP00000326948.2	Q9UET6-1
	FTSJ1	ENST00000898808.1		c.111A>G	p.Gln37Gln	synonymous	Exon 3 of 14	ENSP00000568867.1
	FTSJ1	ENST00000898812.1		c.111A>G	p.Gln37Gln	synonymous	Exon 2 of 13	ENSP00000568871.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1094442 Hom.: 0 Cov.: 30 AF XY: 0.00000555 AC XY: 2 AN XY: 360050

African (AFR) AF: 0.00 AC: 0 AN: 26334

American (AMR) AF: 0.00 AC: 0 AN: 34835

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19325

East Asian (EAS) AF: 0.00 AC: 0 AN: 30116

South Asian (SAS) AF: 0.00 AC: 0 AN: 53493

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40271

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 839964

Other (OTH) AF: 0.00 AC: 0 AN: 45973

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.12
DANN	Benign	0.29
PhyloP100		-2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1556967000; hg19: chrX-48336546;