X-48478577-G-A

Variant names:

• chrX-48478577-G-A
• rs147807045
• NM_012280.4:c.192-40G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012280.4(FTSJ1):​c.192-40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,190,813 control chromosomes in the GnomAD database, including 84 homozygotes. There are 957 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (36 hom., 454 hem., cov: 23)
  • Exomes 𝑓: 0.0018 (48 hom. 503 hem.)
• Consequence: FTSJ1 NM_012280.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.760
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant X-48478577-G-A is Benign according to our data. Variant chrX-48478577-G-A is described in ClinVar as Benign. ClinVar VariationId is 1182161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 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.192-40G>A		intron	N/A	NP_036412.1	A0A024QYX5
	FTSJ1	NM_001441197.1		c.192-40G>A		intron	N/A	NP_001428126.1
	FTSJ1	NM_001441198.1		c.192-40G>A		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.192-40G>A		intron	N/A	ENSP00000326948.2	Q9UET6-1
	FTSJ1	ENST00000898808.1		c.192-40G>A		intron	N/A	ENSP00000568867.1
	FTSJ1	ENST00000898812.1		c.192-40G>A		intron	N/A	ENSP00000568871.1

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 1753 AN: 111576 Hom.: 36 Cov.: 23

Gnomad AFR AF: 0.0542

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00651

Gnomad ASJ AF: 0.000755

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000369

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00478 AC: 843 AN: 176353 AF XY: 0.00332

Gnomad AFR exome AF: 0.0594

Gnomad AMR exome AF: 0.00256

Gnomad ASJ exome AF: 0.000683

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000179

Gnomad OTH exome AF: 0.00161

GnomAD4 exome AF: 0.00176 AC: 1896 AN: 1079186 Hom.: 48 Cov.: 28 AF XY: 0.00145 AC XY: 503 AN XY: 346188

African (AFR) AF: 0.0584 AC: 1521 AN: 26065

American (AMR) AF: 0.00291 AC: 102 AN: 35014

Ashkenazi Jewish (ASJ) AF: 0.000780 AC: 15 AN: 19227

East Asian (EAS) AF: 0.00 AC: 0 AN: 30071

South Asian (SAS) AF: 0.000187 AC: 10 AN: 53439

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40323

Middle Eastern (MID) AF: 0.00297 AC: 12 AN: 4034

European-Non Finnish (NFE) AF: 0.0000763 AC: 63 AN: 825545

Other (OTH) AF: 0.00380 AC: 173 AN: 45468

GnomAD4 genome AF: 0.0157 AC: 1754 AN: 111627 Hom.: 36 Cov.: 23 AF XY: 0.0134 AC XY: 454 AN XY: 33829

African (AFR) AF: 0.0541 AC: 1657 AN: 30628

American (AMR) AF: 0.00650 AC: 69 AN: 10613

Ashkenazi Jewish (ASJ) AF: 0.000755 AC: 2 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3524

South Asian (SAS) AF: 0.000370 AC: 1 AN: 2704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6087

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000132 AC: 7 AN: 52998

Other (OTH) AF: 0.0118 AC: 18 AN: 1524

Alfa AF: 0.00708 Hom.: 37

Bravo AF: 0.0186

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.047
DANN	Benign	0.77
PhyloP100		-0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs147807045; hg19: chrX-48336965;