Variant chrX-48482599-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_012280.4(FTSJ1):c.762A>G(p.Leu254=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,197,987 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 67 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.00021 ( 0 hom. 65 hem. )

Consequence

FTSJ1
NM_012280.4 splice_region, synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.236

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant X-48482599-A-G is Benign according to our data. Variant chrX-48482599-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 129118.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BP7

Synonymous conserved (PhyloP=0.236 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FTSJ1	NM_012280.4 linkuse as main transcript	c.762A>G	p.Leu254=	splice_region_variant, synonymous_variant	11/13	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.762A>G	p.Leu254=	splice_region_variant, synonymous_variant	11/13	1	NM_012280.4	ENSP00000326948	P4	Q9UET6-1

Frequencies

GnomAD3 genomes

AF:

0.000126

AC:

AN:

110836

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

33060

show subpopulations

Gnomad AFR

AF:

0.0000329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000246

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000560

AC:

AN:

160623

Hom.:

AF XY:

0.0000199

AC XY:

AN XY:

50149

show subpopulations

Gnomad AFR exome

AF:

0.0000872

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000209

AC:

227

AN:

1087151

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

AN XY:

354627

show subpopulations

Gnomad4 AFR exome

AF:

0.0000382

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000268

Gnomad4 OTH exome

AF:

0.0000438

GnomAD4 genome

AF:

0.000126

AC:

AN:

110836

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

33060

show subpopulations

Gnomad4 AFR

AF:

0.0000329

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000246

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000144

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 13, 2018	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jun 12, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.67

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