X-48478846-T-C

Position:

• chrX-48478846-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012280.4(FTSJ1):​c.282+139T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.053 in 541,960 control chromosomes in the GnomAD database, including 5,276 homozygotes. There are 7,663 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (3557 hom., 4979 hem., cov: 23)
  • Exomes 𝑓: 0.025 (1719 hom. 2684 hem.)
• Consequence: FTSJ1 NM_012280.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.55

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant X-48478846-T-C is Benign according to our data. Variant chrX-48478846-T-C is described in ClinVar as [Benign]. Clinvar id is 1243336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTSJ1	NM_012280.4	c.282+139T>C		intron_variant		ENST00000348411.3	NP_036412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTSJ1	ENST00000348411.3	c.282+139T>C		intron_variant		1	NM_012280.4	ENSP00000326948	P4

Frequencies

GnomAD3 genomes AF: 0.162 AC: 18124 AN: 111731 Hom.: 3560 Cov.: 23 AF XY: 0.146 AC XY: 4955 AN XY: 33981

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0607

Gnomad ASJ AF: 0.0106

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00184

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0502

Gnomad NFE AF: 0.00337

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.0245 AC: 10550 AN: 430173 Hom.: 1719 AF XY: 0.0196 AC XY: 2684 AN XY: 136673

Gnomad4 AFR exome AF: 0.563

Gnomad4 AMR exome AF: 0.0369

Gnomad4 ASJ exome AF: 0.0139

Gnomad4 EAS exome AF: 0.0000407

Gnomad4 SAS exome AF: 0.00186

Gnomad4 FIN exome AF: 0.000140

Gnomad4 NFE exome AF: 0.00274

Gnomad4 OTH exome AF: 0.0539

GnomAD4 genome AF: 0.162 AC: 18150 AN: 111787 Hom.: 3557 Cov.: 23 AF XY: 0.146 AC XY: 4979 AN XY: 34047

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.0606

Gnomad4 ASJ AF: 0.0106

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00222

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00337

Gnomad4 OTH AF: 0.128

Alfa AF: 0.127 Hom.: 1302

Bravo AF: 0.187

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs5952506; hg19: chrX-48337234;