rs370849542

Variant names:

• chrX-48478629-C-T
• rs370849542
• NM_012280.4:c.204C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_012280.4(FTSJ1):​c.204C>T​(p.Ser68Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000034 in 1,205,983 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 19 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000037 (0 hom. 19 hem.)
• Consequence: FTSJ1 NM_012280.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant X-48478629-C-T is Benign according to our data. Variant chrX-48478629-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1785028.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 19 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.204C>T	p.Ser68Ser	synonymous	Exon 4 of 13	NP_036412.1	A0A024QYX5
	FTSJ1	NM_001441197.1		c.204C>T	p.Ser68Ser	synonymous	Exon 4 of 11	NP_001428126.1
	FTSJ1	NM_001441198.1		c.204C>T	p.Ser68Ser	synonymous	Exon 5 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.204C>T	p.Ser68Ser	synonymous	Exon 4 of 13	ENSP00000326948.2	Q9UET6-1
	FTSJ1	ENST00000898808.1		c.204C>T	p.Ser68Ser	synonymous	Exon 5 of 14	ENSP00000568867.1
	FTSJ1	ENST00000898812.1		c.204C>T	p.Ser68Ser	synonymous	Exon 4 of 13	ENSP00000568871.1

Frequencies

GnomAD3 genomes AF: 0.00000896 AC: 1 AN: 111665 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000563 AC: 10 AN: 177680 AF XY: 0.000127

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: 0.0000253

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000366 AC: 40 AN: 1094266 Hom.: 0 Cov.: 30 AF XY: 0.0000528 AC XY: 19 AN XY: 359856

African (AFR) AF: 0.00 AC: 0 AN: 26349

American (AMR) AF: 0.00 AC: 0 AN: 35071

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19329

East Asian (EAS) AF: 0.00 AC: 0 AN: 30162

South Asian (SAS) AF: 0.000447 AC: 24 AN: 53735

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40390

Middle Eastern (MID) AF: 0.000243 AC: 1 AN: 4120

European-Non Finnish (NFE) AF: 0.0000179 AC: 15 AN: 839159

Other (OTH) AF: 0.00 AC: 0 AN: 45951

GnomAD4 genome AF: 0.00000895 AC: 1 AN: 111717 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33931

African (AFR) AF: 0.00 AC: 0 AN: 30724

American (AMR) AF: 0.00 AC: 0 AN: 10626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3530

South Asian (SAS) AF: 0.00 AC: 0 AN: 2699

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52997

Other (OTH) AF: 0.00 AC: 0 AN: 1520

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.36
DANN	Benign	0.64
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs370849542; hg19: chrX-48337017;