Variant X-48478695-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000348411.3(FTSJ1):c.270G>T(p.Gly90=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,193,698 control chromosomes in the GnomAD database, including 2 homozygotes. There are 426 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., 83 hem., cov: 23)

Exomes 𝑓: 0.00093 ( 1 hom. 343 hem. )

Consequence

FTSJ1
ENST00000348411.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.107

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant X-48478695-G-T is Benign according to our data. Variant chrX-48478695-G-T is described in ClinVar as [Benign]. Clinvar id is 197290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-48478695-G-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.107 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 83 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTSJ1	NM_012280.4 linkuse as main transcript	c.270G>T	p.Gly90=	synonymous_variant	4/13	ENST00000348411.3	NP_036412.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FTSJ1	ENST00000348411.3 linkuse as main transcript	c.270G>T	p.Gly90=	synonymous_variant	4/13	1	NM_012280.4	ENSP00000326948	P4	Q9UET6-1

Frequencies

GnomAD3 genomes

AF:

0.00262

AC:

295

AN:

112399

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

AN XY:

34561

show subpopulations

Gnomad AFR

AF:

0.00704

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00234

Gnomad ASJ

AF:

0.00640

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.000527

Gnomad OTH

AF:

0.00398

GnomAD3 exomes

AF:

0.00137

AC:

240

AN:

174682

Hom.:

AF XY:

0.00106

AC XY:

AN XY:

60272

show subpopulations

Gnomad AFR exome

AF:

0.00576

Gnomad AMR exome

AF:

0.00172

Gnomad ASJ exome

AF:

0.00941

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000516

Gnomad OTH exome

AF:

0.00300

GnomAD4 exome

AF:

0.000927

AC:

1002

AN:

1081248

Hom.:

Cov.:

AF XY:

0.000986

AC XY:

343

AN XY:

347790

show subpopulations

Gnomad4 AFR exome

AF:

0.00765

Gnomad4 AMR exome

AF:

0.00206

Gnomad4 ASJ exome

AF:

0.00810

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000564

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000509

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.00261

AC:

293

AN:

112450

Hom.:

Cov.:

AF XY:

0.00240

AC XY:

AN XY:

34622

show subpopulations

Gnomad4 AFR

AF:

0.00696

Gnomad4 AMR

AF:

0.00234

Gnomad4 ASJ

AF:

0.00640

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000527

Gnomad4 OTH

AF:

0.00393

Alfa

AF:

0.00291

Hom.:

Bravo

AF:

0.00337

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 18, 2015

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.0

DANN

Benign

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over