chrX-48481624-C-G

Variant names:

• chrX-48481624-C-G
• rs73483894
• NM_012280.4:c.572-8C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012280.4(FTSJ1):​c.572-8C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000933 in 1,071,906 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts 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: not found (cov: 24)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
• Consequence: FTSJ1 NM_012280.4 splice_region, intron
• Scores: Splicing: ADA: 0.0006499
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTSJ1	NM_012280.4	c.572-8C>G		splice_region_variant, intron_variant	Intron 8 of 12	ENST00000348411.3	NP_036412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTSJ1	ENST00000348411.3	c.572-8C>G		splice_region_variant, intron_variant	Intron 8 of 12	1	NM_012280.4	ENSP00000326948.2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00000552 AC: 1 AN: 181224 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.33e-7 AC: 1 AN: 1071906 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 340400

African (AFR) AF: 0.00 AC: 0 AN: 25909

American (AMR) AF: 0.00 AC: 0 AN: 35148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19214

East Asian (EAS) AF: 0.00 AC: 0 AN: 30075

South Asian (SAS) AF: 0.00 AC: 0 AN: 53439

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40499

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4069

European-Non Finnish (NFE) AF: 0.00000122 AC: 1 AN: 818308

Other (OTH) AF: 0.00 AC: 0 AN: 45245

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 26

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00065
dbscSNV1_RF	Benign	0.080
SpliceAI score (max)		0.090		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: rs73483894; hg19: chrX-48340012;