NM_012280.4:c.572-8C>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012280.4(FTSJ1):​c.572-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00492 in 1,184,495 control chromosomes in the GnomAD database, including 185 homozygotes. There are 1,507 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (88 hom., 812 hem., cov: 24)
  • Exomes 𝑓: 0.0026 (97 hom. 695 hem.)
• Consequence: FTSJ1 NM_012280.4 splice_region, intron
• Scores: Splicing: ADA: 0.00006619
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-48481624-C-T is Benign according to our data. Variant chrX-48481624-C-T is described in ClinVar as Benign. ClinVar VariationId is 129117.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

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.572-8C>T		splice_region intron	N/A	NP_036412.1
	FTSJ1	NM_001441197.1		c.572-8C>T		splice_region intron	N/A	NP_001428126.1
	FTSJ1	NM_001441198.1		c.572-8C>T		splice_region intron	N/A	NP_001428127.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FTSJ1	ENST00000348411.3	TSL:1 MANE Select	c.572-8C>T		splice_region intron	N/A	ENSP00000326948.2
	FTSJ1	ENST00000898808.1		c.572-8C>T		splice_region intron	N/A	ENSP00000568867.1
	FTSJ1	ENST00000898812.1		c.572-8C>T		splice_region intron	N/A	ENSP00000568871.1

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 2998 AN: 112554 Hom.: 89 Cov.: 24

Gnomad AFR AF: 0.0913

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000359

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00840

Gnomad NFE AF: 0.000300

Gnomad OTH AF: 0.0190

GnomAD2 exomes AF: 0.00789 AC: 1429 AN: 181224 AF XY: 0.00469

Gnomad AFR exome AF: 0.0977

Gnomad AMR exome AF: 0.00466

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000149

Gnomad OTH exome AF: 0.00536

GnomAD4 exome AF: 0.00264 AC: 2829 AN: 1071888 Hom.: 97 Cov.: 28 AF XY: 0.00204 AC XY: 695 AN XY: 340398

African (AFR) AF: 0.0876 AC: 2268 AN: 25896

American (AMR) AF: 0.00572 AC: 201 AN: 35147

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

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

South Asian (SAS) AF: 0.0000561 AC: 3 AN: 53439

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

Middle Eastern (MID) AF: 0.00369 AC: 15 AN: 4069

European-Non Finnish (NFE) AF: 0.000103 AC: 84 AN: 818308

Other (OTH) AF: 0.00570 AC: 258 AN: 45241

GnomAD4 genome AF: 0.0266 AC: 2998 AN: 112607 Hom.: 88 Cov.: 24 AF XY: 0.0234 AC XY: 812 AN XY: 34769

African (AFR) AF: 0.0912 AC: 2826 AN: 31001

American (AMR) AF: 0.0116 AC: 124 AN: 10700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3570

South Asian (SAS) AF: 0.000360 AC: 1 AN: 2779

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6212

Middle Eastern (MID) AF: 0.00926 AC: 2 AN: 216

European-Non Finnish (NFE) AF: 0.000300 AC: 16 AN: 53245

Other (OTH) AF: 0.0188 AC: 29 AN: 1545

Alfa AF: 0.00468 Hom.: 26

Bravo AF: 0.0313

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.60
DANN	Benign	0.66
PhyloP100		0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000066
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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;