X-48476947-A-G

Variant names:

• chrX-48476947-A-G
• rs2268954
• NM_012280.4:c.-88+551A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012280.4(FTSJ1):​c.-88+551A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 108,879 control chromosomes in the GnomAD database, including 1,819 homozygotes. There are 6,207 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: 𝑓 0.20 (1819 hom., 6207 hem., cov: 21)
• Consequence: FTSJ1 NM_012280.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.944
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FTSJ1	NM_012280.4	c.-88+551A>G		intron_variant	Intron 1 of 12	ENST00000348411.3	NP_036412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FTSJ1	ENST00000348411.3	c.-88+551A>G		intron_variant	Intron 1 of 12	1	NM_012280.4	ENSP00000326948.2

Frequencies

GnomAD3 genomes AF: 0.202 AC: 21994 AN: 108827 Hom.: 1824 Cov.: 21

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.202 AC: 21994 AN: 108879 Hom.: 1819 Cov.: 21 AF XY: 0.198 AC XY: 6207 AN XY: 31307

African (AFR) AF: 0.193 AC: 5753 AN: 29845

American (AMR) AF: 0.299 AC: 3039 AN: 10171

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 456 AN: 2610

East Asian (EAS) AF: 0.455 AC: 1542 AN: 3387

South Asian (SAS) AF: 0.375 AC: 951 AN: 2533

European-Finnish (FIN) AF: 0.155 AC: 869 AN: 5598

Middle Eastern (MID) AF: 0.141 AC: 30 AN: 213

European-Non Finnish (NFE) AF: 0.170 AC: 8899 AN: 52343

Other (OTH) AF: 0.221 AC: 333 AN: 1505

Alfa AF: 0.195 Hom.: 8980

Bravo AF: 0.221

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.8
DANN	Benign	0.79
PhyloP100		0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2268954; hg19: chrX-48335335;