rs183649523

chrX-48482397-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_012280.4(FTSJ1):c.656-6C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,178,033 control chromosomes in the GnomAD database, including 2 homozygotes. There are 89 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00036 (0 hom., 15 hem., cov: 22)
  • Exomes 𝑓: 0.00022 (2 hom. 74 hem.)
• Consequence: FTSJ1 NM_012280.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.002054
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0530

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant X-48482397-C-G is Benign according to our data. Variant chrX-48482397-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 445581.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 15 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTSJ1	NM_012280.4	c.656-6C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000348411.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTSJ1	ENST00000348411.3	c.656-6C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_012280.4	P4

Frequencies

GnomAD3 genomes AF: 0.000361 AC: 40 AN: 110776 Hom.: 0 Cov.: 22 AF XY: 0.000455 AC XY: 15 AN XY: 32990

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000192

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0103

Gnomad SAS AF: 0.000382

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000189

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000942 AC: 169 AN: 179499 Hom.: 2 AF XY: 0.000794 AC XY: 51 AN XY: 64201

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0120

Gnomad SAS exome AF: 0.0000548

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000125

Gnomad OTH exome AF: 0.000449

GnomAD4 exome AF: 0.000222 AC: 237 AN: 1067205 Hom.: 2 Cov.: 27 AF XY: 0.000219 AC XY: 74 AN XY: 337971

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00678

Gnomad4 SAS exome AF: 0.0000754

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000123

Gnomad4 OTH exome AF: 0.000599

GnomAD4 genome AF: 0.000361 AC: 40 AN: 110828 Hom.: 0 Cov.: 22 AF XY: 0.000454 AC XY: 15 AN XY: 33052

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000192

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0103

Gnomad4 SAS AF: 0.000383

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000189

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000130 Hom.: 1

Bravo AF: 0.000544

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Mar 29, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	12
Dann	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0021
dbscSNV1_RF	Benign	0.22
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: -36

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs183649523; hg19: chrX-48340785;