X-48478695-G-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_012280.4(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 NM_012280.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.107

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 -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 GnomAd at 85 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FTSJ1	NM_012280.4	c.270G>T	p.Gly90=	synonymous_variant	4/13	ENST00000348411.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FTSJ1	ENST00000348411.3	c.270G>T	p.Gly90=	synonymous_variant	4/13	1	NM_012280.4	P4

Frequencies

GnomAD3 genomes AF: 0.00262 AC: 295 AN: 112399 Hom.: 1 Cov.: 23 AF XY: 0.00246 AC XY: 85 AN XY: 34561

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.: 0 AF XY: 0.00106 AC XY: 64 AN XY: 60272

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.: 1 Cov.: 29 AF XY: 0.000986 AC XY: 343 AN XY: 347790

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.: 1 Cov.: 23 AF XY: 0.00240 AC XY: 83 AN XY: 34622

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.: 13

Bravo AF: 0.00337

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

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

Other links and lift over

dbSNP: rs138008946; hg19: chrX-48337083;