rs2070991

chrX-48481597-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012280.4(FTSJ1):c.572-35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,146,737 control chromosomes in the GnomAD database, including 21,056 homozygotes. There are 82,322 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (2302 hom., 7789 hem., cov: 23)
  • Exomes 𝑓: 0.22 (18754 hom. 74533 hem.)
• Consequence: FTSJ1 NM_012280.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00200

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant X-48481597-C-T is Benign according to our data. Variant chrX-48481597-C-T is described in ClinVar as [Benign]. Clinvar id is 1285660.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTSJ1	NM_012280.4	c.572-35C>T		intron_variant		ENST00000348411.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTSJ1	ENST00000348411.3	c.572-35C>T		intron_variant		1	NM_012280.4	P4

Frequencies

GnomAD3 genomes AF: 0.231 AC: 25860 AN: 111801 Hom.: 2304 Cov.: 23 AF XY: 0.229 AC XY: 7778 AN XY: 34027

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.148

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.243

GnomAD3 exomes AF: 0.263 AC: 47020 AN: 179091 Hom.: 4679 AF XY: 0.257 AC XY: 16468 AN XY: 63981

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.208

Gnomad EAS exome AF: 0.471

Gnomad SAS exome AF: 0.351

Gnomad FIN exome AF: 0.168

Gnomad NFE exome AF: 0.192

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.224 AC: 232085 AN: 1034885 Hom.: 18754 Cov.: 25 AF XY: 0.237 AC XY: 74533 AN XY: 314697

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.374

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.201

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.231 AC: 25860 AN: 111852 Hom.: 2302 Cov.: 23 AF XY: 0.228 AC XY: 7789 AN XY: 34088

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.243

Alfa AF: 0.211 Hom.: 1828

Bravo AF: 0.250

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.1
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2070991; hg19: chrX-48339985; COSMIC: COSV50025579; COSMIC: COSV50025579;